Summary of interactions between bacteria and platelets. Bacteria can either interact with platelets directly or indirectly using a bridging protein, thus triggering activation. ClfA; clumping factor A, FnbpA; fibronectin binding protein A, SpA; protein A, PadA; platelet adhesion protein A, IsdB; iron-regulated surface determinant B, SdrG; Serine aspartate repeat G, Hsa; haemaglutinin salivary antigen, GspB; glycosylated spretococcal protein B, SrpA; serine rich protein A, IgG; immunoglobulin G, vWf; vonWillebrand Factor, C1q; complement 1q, GP; glycoprotein, TLR; Toll like receptor
1. Introduction
It is well established that the primary function of platelets is their adhesion to endothelium or to matrix protein components at sites of the injured vessel wall in the initiation of haemostasis [1].Despite this critical role, platelets are poorly appreciated for their involvement in inflammatory or immune processes associated with host defence. The concept that platelets interact with bacteria is not new as there are many reports published throughout history describing this interaction. For example, the earliest report by Levaditi in 1901 demonstrated that platelets activated and ‘clumped’ when
As our knowledge of basic platelet biology developed in more modern times it has become apparent that platelets are powerful multifunctional cells that are involved in processes outside their traditional role of thrombosis and haemostasis. For example, platelets share many similarities with professional leukocytes (white blood cells) well characterised for their role in immuno-protection following invasion by foreign invaders. Platelets can also recognise foreign invaders through specific receptors, release their granule contents and recruit immune cells.
Recently human platelets have been shown to express Toll Like Receptor (TLR) 1, 2, 4, 6, 8 and 9 [8-13]. These type I integral membrane receptors recognise common pathogen-associated molecular patterns found in foreign invaders. Platelets also express Intracellular Cell Adhesion Molecular (ICAM) 2 which binds to leukocyte β2 integrin, LFA-1 (α1β2, CD11a/CD18) and to dendritic cell specific ICAM grabbing nonintegrin (DC-SIGN). Trans interactions of platelet-derived Junctional Adhesion Molecules (A and C) have been found to support the luminal deposition of platelet chemokines and to enhance the recruitment of leukocytes. Upon activation CD40L is upregulated on the platelet surface which results in stimulation of endothelial cells through its cognate receptor CD40 and in increased expression of adhesion molecules, release of chemokines (eg. RANTES) enhancing recruitment of leukocytes [14].
As a result of such receptor mediated interactions platelets can secrete granular contents which have significant immuno-modulatory effects. Alpha granules contain proteins such as P-selectin which mediates adhesion of platelets to monocytes, neutrophils and lymphocytes, resulting in the formation of platelet leukocyte complexes [15-17]. Secretion also results in release of many chemotactic agents which lead to the recruitment of various inflammatory cells; platelet derived growth factor (PDGF) and 12-hydroxyeicosatetraenoic acid (12-HETE) which recruit neutrophils [18, 19]; platelet factor 4 and platelet derived histamine releasing factor (PDHRF) which recruit eosinophils in airway disease [20, 21]; PDGF and transforming growth factor β (TGF-β) which recruit monocytes and macrophages and TGF-β which recruits fibroblasts [22-24]. In addition the alpha granules also release many antimicrobial peptides such as beta-lysin, platelet microbial protein (PMP), neutrophil activating peptide (NAP-2), released upon activation normal T-cell expressed and secreted (RANTES) and fibrinopeptides A and B [25-29].
2. Common observations in platelet-bacterial interactions
Unlike typical platelet agonists that bind to specific platelet receptors and trigger a response, bacteria can interact with platelets using a number of different mechanisms.
Bacterial induced platelet aggregation is different in some respects to that seen with other platelet agonists. Bacterial-induced aggregation is an all-or-nothing response, in that no matter what concentration of bacteria are added to a platelet preparation the extent of aggregation will always be maximal (often less than that seen with other agonists) or else there is no aggregation. Unlike other agonists there is a lag time to aggregation. Adjusting the concentration of bacteria shortens the lag time to a minimum but never eliminates it. There are two categories of bacteria: those that have a short lag time of around 2-5 mins e.g.
Bacteria can finally support platelet adhesion, induce platelet spreading or trigger platelet aggregation and these interactions are often mediated by different platelet receptors and bacterial proteins. For example,
3. Platelet receptors recognised by bacteria
3.1. Glycoprotein Ibα
3.1.1. Direct interaction with GPIbα
3.1.2. Indirect interaction with GPIbα
Additional studies identified that bacterial interaction with platelets was abolished when plasma was removed, suggestive of the need for a plasma protein in the interaction. Subsequent studies identified that a number of bacteria bind vWf and bridge the bacteria to platelet GPIbα. For example,
3.2. Glycoprotein IIbIIIa
3.2.1. Direct interaction with GPIIbIIIa
A number of different species of bacteria have been shown to bind directly to GPIIbIIIa. Physiological ligands mediate attachment to GPIIbIIIa via a short amino acid sequence, RGD. Consistent with this observation, several bacterial proteins have been identified to express an RGD-like sequence in their cell wall proteins. The serine/aspartate (SD) repeat family of proteins are among the most important cell wall components expressed on the surface of the skin commensal
Under iron limited conditions
3.2.2. Indirect interaction with GPIIbIIIa
Both staphylococci and streptococci express a number of plasma protein binding proteins on their surface. Probably the most common are fibrinogen binding proteins, often expressed at different phase of bacterial growth. For example,
The ligand binding sites of ClfA and ClfB have been mapped to residues 220 to 559 [55]. Interestingly the ligand binding sites of the two homologs are only 27% identical. In contrast to ClfA which recognises the extreme C-terminus of the γ-chain of fibrinogen, ClfB recognises the α-chain of fibrinogen [56, 57]. The FnBPA or FnBPB can bind either fibronectin or fibrinogen. The N-terminal region of the fibronectin binding proteins (N1, N2 and N3) is structurally and functionally similar to the clumping factors, however in place of the serine-aspartate repeat region are tandemly repeated fibronectin-binding repeat domains. The FnBP’s bind fibrinogen via the N1, N2 and N3 domains and fibronectin via the repeat domains (11 in FnBPA and 10 in FnBPB) [58]. SdrG (
Group A streptococci (
A common observation is beginning to unfold in the light of all the fibrinogen binding proteins expressed on bacteria. Results demonstrate that where a bacterial protein binds fibrinogen and crosslinks to platelet GPIIbIIIa it is usually not enough to trigger an activating signal in the platelet and usually requires a co-stimulus In all cases outlined above the key co-stimulus is provided by the bacteria binding IgG and cross linking to its reciprocal receptor on platelets, FcγRIIa.
3.3. FcγRIIA
3.3.1. Direct interaction with FcγRIIA
Currently there are no reports of a bacterial protein binding directly to FcγRIIa on platelets, however there are a number of reports of an indirect interaction where bacterial proteins use IgG to cross link to platelet FcγRIIA.
3.3.2. Indirect interaction with FcγRIIA
FcγRIIA is fast becoming the most important receptor in platelet bacterial interactions as it has been shown to inhibit all bacterial induced platelet activation including those triggered by
|
|
|
|
GPIbα |
|
Direct | 42,43,44 |
|
Direct | 30,94 | |
|
? | 46 | |
|
vWf | 47 | |
|
vWf | 48 | |
GPIIbIIIa |
|
Direct | 49,50 |
|
Direct | 51 | |
|
Direct | 52,53,54 | |
|
Fibrinogen | 55,56 | |
|
Fibrinogen | 57 | |
|
Fibronectin | 58 | |
|
Fibrinogen | 59,60 | |
|
Fibrinogen | 62,63 | |
|
Fibrinogen | 64,65 | |
FcγRIIa |
|
IgG | 33 |
|
IgG | 36 | |
|
IgG | 72 | |
|
IgG | 50 | |
|
IgG | 34 | |
|
IgG | 73 | |
gC1q-R/P32 |
|
direct | 74,75 |
|
? | 32, 36 | |
|
? | 32,72 | |
|
? | 38,77 | |
TLR2 |
|
direct | 67 |
|
direct | 79 |
|
|
|
|
TLR4 |
|
LPS | 81,82,83,84 |
? |
|
LTA | 85,86,87,88 |
? |
|
Gingipains | 39,89 |
Glycospingolipids |
|
Verotoxin | 41,90 |
? |
|
α-toxin | 91,92 |
All published reports of streptococcal induced platelet aggregation demonstrate their ability to induce platelet aggregation in an FcγRIIa dependent manner. Early reports suggested that streptococci could induce platelet aggregation in the absence of plasma proteins. However regardless of this, blocking FcγRIIa with a monoclonal antibody still abolished aggregation [30], suggesting that FcγRIIa may be playing a role in signal amplification. This observation is analogous to the role of FcγRIIa in promoting cell signalling/amplification through various platelets receptors such as GPIIbIIIa and GPIbα. Another oral bacteria,
Oral bacteria,
3.4. gC1q-R/P33
3.4.1. Direct interaction with gC1q-R/P33
3.4.2. Indirect interaction
Complement is part of the immune system that augments the opsonisation of bacteria by antibodies which in turn facilitates phagocytosis. There are three main pathways that lead to complement activation; the classical pathway can be triggered by antigen-antibody complexes; the alternative pathway can be triggered by binding specific complement proteins binding to the bacterial surface and finally the lectin pathway can be triggered by mannose binding protein binding the bacterial surface [76]. The lag time to platelet aggregation in response to
The lag time to platelet aggregation varies with different strains of
3.5. Toll like receptor 2
3.5.1. Direct interaction with TLR2
4. Secreted products
Lipopolysaccharide (LPS) is shed from the cell wall of gram negative bacteria into the local milieu and interacts with Toll-like receptors (TLR) on immune cells [80].
In contrast Lipoteichoic acid (LTA) is secreted by Gram-positive bacteria. LTA binds to platelets and inhibits platelet aggregation by collagen [85]. LTA also supports platelet adhesion to
In a manner similar to thrombin activation of the Protease Activated Receptors on the platelet surface,
5. Animal studies versus clinically relevant models of infection
There are many reports in the literature investigating the interaction between bacteria and platelets
One potential possibility to overcome this problem is to develop a more clinically relevant model of infection using physiological conditions with human platelets. Using a parallel flow chamber with human platelets and shear conditions experienced under human physiological conditions a number of key interactions were observed. Under fluid shear conditions, human platelets rolled on immobilised
6. Conclusion
Although the field of platelet bacterial interactions is in its infancy, significant advances have been made in identifying some of the molecular mechanisms. Through learning about these interactions it has provided strong evidence that platelets may indeed be acting as primitive immune cells. However a lot more research is required to gain a better understanding of the exact role platelets play in in the process. For example, by adhering, aggregating, spreading or forming a thrombus on the bacteria are the platelets trying to restrict spread of infection and then by releasing their granular contents orchestrate or control the immune response to the infection by recruiting defined numbers of leukocytes. Alternatively is it a clever move by the bacteria who coat themselves in non-professional immune cells (platelets) and therefore rendering themselves safe from attack from professional immune cells (leukocytes) and antibiotics, which cannot penetrate the platelet encapsulation to kill the bacteria thus allowing them to grow and divide in a safe environment.
References
- 1.
Ruggeri, Z. M. (2009) Platelet adhesion under flow, Microcirculation 16 , 58-83. - 2.
Levaditi, C. (1901) Et des organism vaccines contre le vibron cholerique, Ann Inst Pasteur 15 , 894-924. - 3.
Dudgeon LS, G. H. (1931) The examination of the tissues and some observations on the blood platelets of rabbits at intervals of five minutes and later after intraveneous inoculations of Staphylococcus aureus and India ink, J. Hyg (camb) 31 . - 4.
Clawson, C. C., and White, J. G. (1971) Platelet interaction with bacteria. I. Reaction phases and effects of inhibitors, The American journal of pathology 65 , 367-380. - 5.
Clawson, C. C., and White, J. G. (1971) Platelet interaction with bacteria. II. Fate of the bacteria, The American journal of pathology 65 , 381-397. - 6.
Clawson, C. C. (1973) Platelet interaction with bacteria. 3. Ultrastructure, The American journal of pathology 70 , 449-471. - 7.
Clawson, C. C., Rao, G. H., and White, J. G. (1975) Platelet interaction with bacteria. IV. Stimulation of the release reaction, The American journal of pathology 81 , 411-420. - 8.
Cognasse, F., Hamzeh, H., Chavarin, P., Acquart, S., Genin, C., and Garraud, O. (2005) Evidence of Toll-like receptor molecules on human platelets, Immunology and cell biology 83 , 196-198. - 9.
Shiraki, R., Inoue, N., Kawasaki, S., Takei, A., Kadotani, M., Ohnishi, Y., Ejiri, J., Kobayashi, S., Hirata, K., Kawashima, S., and Yokoyama, M. (2004) Expression of Toll-like receptors on human platelets, Thrombosis research 113 , 379-385. - 10.
Aslam, R., Speck, E. R., Kim, M., Crow, A. R., Bang, K. W., Nestel, F. P., Ni, H., Lazarus, A. H., Freedman, J., and Semple, J. W. (2006) Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo, Blood 107 , 637-641. - 11.
Zhang, G., Han, J., Welch, E. J., Ye, R. D., Voyno-Yasenetskaya, T. A., Malik, A. B., Du, X., and Li, Z. (2009) Lipopolysaccharide stimulates platelet secretion and potentiates platelet aggregation via TLR4/MyD88 and the cGMP-dependent protein kinase pathway, Journal of immunology 182 , 7997-8004. - 12.
Garraud, O., and Cognasse, F. (2010) Platelet Toll-like receptor expression: the link between "danger" ligands and inflammation, Inflammation & allergy drug targets 9 , 322-333. - 13.
Andonegui, G., Kerfoot, S. M., McNagny, K., Ebbert, K. V., Patel, K. D., and Kubes, P. (2005) Platelets express functional Toll-like receptor-4, Blood 106 , 2417-2423. - 14.
von Hundelshausen, P., and Weber, C. (2007) Platelets as immune cells: bridging inflammation and cardiovascular disease, Circulation research 100 , 27-40. - 15.
Diacovo, T. G., Puri, K. D., Warnock, R. A., Springer, T. A., and von Andrian, U. H. (1996) Platelet-mediated lymphocyte delivery to high endothelial venules, Science 273 , 252-255. - 16.
Diacovo, T. G., Roth, S. J., Buccola, J. M., Bainton, D. F., and Springer, T. A. (1996) Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18, Blood 88 , 146-157. - 17.
Larsen, E., Celi, A., Gilbert, G. E., Furie, B. C., Erban, J. K., Bonfanti, R., Wagner, D. D., and Furie, B. (1989) PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes, Cell 59 , 305-312. - 18.
Herd, C. M., and Page, C. P. (1994) Pulmonary immune cells in health and disease: platelets, Eur Respir J 7 , 1145-1160. - 19.
Mannaioni, P. F., Di Bello, M. G., and Masini, E. (1997) Platelets and inflammation: role of platelet-derived growth factor, adhesion molecules and histamine, Inflamm Res 46 , 4-18. - 20.
Brindley, L. L., Sweet, J. M., and Goetzl, E. J. (1983) Stimulation of histamine release from human basophils by human platelet factor 4, J Clin Invest 72 , 1218-1223. - 21.
Frigas, E., and Gleich, G. J. (1986) The eosinophil and the pathophysiology of asthma, J Allergy Clin Immunol 77 , 527-537. - 22.
Deuel, T. F., Senior, R. M., Huang, J. S., and Griffin, G. L. (1982) Chemotaxis of monocytes and neutrophils to platelet-derived growth factor, J Clin Invest 69 , 1046-1049. - 23.
Tzeng, D. Y., Deuel, T. F., Huang, J. S., and Baehner, R. L. (1985) Platelet-derived growth factor promotes human peripheral monocyte activation, Blood 66 , 179-183. - 24.
Wahl, S. M., Hunt, D. A., Wakefield, L. M., McCartney-Francis, N., Wahl, L. M., Roberts, A. B., and Sporn, M. B. (1987) Transforming growth factor type beta induces monocyte chemotaxis and growth factor production, Proc Natl Acad Sci U S A 84 , 5788-5792. - 25.
Johnson, F. B., and Donaldson, D. M. (1968) Purification of staphylocidal beta-lysin from rabbit serum, J Bacteriol 96 , 589-595. - 26.
Donaldson, D. M., and Tew, J. G. (1977) beta-Lysin of platelet origin, Bacteriol Rev 41 , 501-513. - 27.
Kameyoshi, Y., Dorschner, A., Mallet, A. I., Christophers, E., and Schroder, J. M. (1992) Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils, J Exp Med 176 , 587-592. - 28.
Yeaman, M. R., Tang, Y. Q., Shen, A. J., Bayer, A. S., and Selsted, M. E. (1997) Purification and in vitro activities of rabbit platelet microbicidal proteins, Infect Immun 65 , 1023-1031. - 29.
Krijgsveld, J., Zaat, S. A., Meeldijk, J., van Veelen, P. A., Fang, G., Poolman, B., Brandt, E., Ehlert, J. E., Kuijpers, A. J., Engbers, G. H., Feijen, J., and Dankert, J. (2000) Thrombocidins, microbicidal proteins from human blood platelets, are C-terminal deletion products of CXC chemokines, J Biol Chem 275 , 20374-20381. - 30.
Kerrigan, S. W., Douglas, I., Wray, A., Heath, J., Byrne, M. F., Fitzgerald, D., and Cox, D. (2002) A role for glycoprotein Ib in Streptococcus sanguis-induced platelet aggregation, Blood 100 , 509-516. - 31.
Waller, A. K., Sage, T., Kumar, C., Carr, T., Gibbins, J. M., and Clarke, S. R. (2013) Staphylococcus aureus lipoteichoic acid inhibits platelet activation and thrombus formation via the Paf receptor, The Journal of infectious diseases 208 , 2046-2057. - 32.
O'Brien, L., Kerrigan, S. W., Kaw, G., Hogan, M., Penades, J., Litt, D., Fitzgerald, D. J., Foster, T. J., and Cox, D. (2002) Multiple mechanisms for the activation of human platelet aggregation by Staphylococcus aureus: roles for the clumping factors ClfA and ClfB, the serine-aspartate repeat protein SdrE and protein A, Molecular microbiology 44 , 1033-1044. - 33.
Fitzgerald, J. R., Loughman, A., Keane, F., Brennan, M., Knobel, M., Higgins, J., Visai, L., Speziale, P., Cox, D., and Foster, T. J. (2006) Fibronectin-binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the FcgammaRIIa receptor, Molecular microbiology 59 , 212-230. - 34.
Byrne, M. F., Kerrigan, S. W., Corcoran, P. A., Atherton, J. C., Murray, F. E., Fitzgerald, D. J., and Cox, D. M. (2003) Helicobacter pylori binds von Willebrand factor and interacts with GPIb to induce platelet aggregation, Gastroenterology 124 , 1846-1854. - 35.
Fitzgerald, J. R., Foster, T. J., and Cox, D. (2006) The interaction of bacterial pathogens with platelets, Nat Rev Microbiol 4 , 445-457. - 36.
Loughman, A., Fitzgerald, J. R., Brennan, M. P., Higgins, J., Downer, R., Cox, D., and Foster, T. J. (2005) Roles for fibrinogen, immunoglobulin and complement in platelet activation promoted by Staphylococcus aureus clumping factor A, Molecular microbiology 57 , 804-818. - 37.
Ford, I., Douglas, C. W., Cox, D., Rees, D. G., Heath, J., and Preston, F. E. (1997) The role of immunoglobulin G and fibrinogen in platelet aggregation by Streptococcus sanguis, Br J Haematol 97 , 737-746. - 38.
Ford, I., Douglas, C. W., Heath, J., Rees, C., and Preston, F. E. (1996) Evidence for the involvement of complement proteins in platelet aggregation by Streptococcus sanguis NCTC 7863, British journal of haematology 94 , 729-739. - 39.
Lourbakos, A., Yuan, Y. P., Jenkins, A. L., Travis, J., Andrade-Gordon, P., Santulli, R., Potempa, J., and Pike, R. N. (2001) Activation of protease-activated receptors by gingipains from Porphyromonas gingivalis leads to platelet aggregation: a new trait in microbial pathogenicity, Blood 97 , 3790-3797. - 40.
Proulx, F., Seidman, E. G., and Karpman, D. (2001) Pathogenesis of Shiga toxin-associated hemolytic uremic syndrome, Pediatr Res 50 , 163-171. - 41.
Cooling, L. L., Walker, K. E., Gille, T., and Koerner, T. A. (1998) Shiga toxin binds human platelets via globotriaosylceramide (Pk antigen) and a novel platelet glycosphingolipid, Infect Immun 66 , 4355-4366. - 42.
Kerrigan, S. W., Jakubovics, N. S., Keane, C., Maguire, P., Wynne, K., Jenkinson, H. F., and Cox, D. (2007) Role of Streptococcus gordonii surface proteins SspA/SspB and Hsa in platelet function, Infection and immunity 75 , 5740-5747. - 43.
Bensing, B. A., Lopez, J. A., and Sullam, P. M. (2004) The Streptococcus gordonii surface proteins GspB and Hsa mediate binding to sialylated carbohydrate epitopes on the platelet membrane glycoprotein Ibalpha, Infection and immunity 72 , 6528-6537. - 44.
Takamatsu, D., Bensing, B. A., Cheng, H., Jarvis, G. A., Siboo, I. R., Lopez, J. A., Griffiss, J. M., and Sullam, P. M. (2005) Binding of the Streptococcus gordonii surface glycoproteins GspB and Hsa to specific carbohydrate structures on platelet membrane glycoprotein Ibalpha, Molecular microbiology 58 , 380-392. - 45.
Pyburn, T. M., Bensing, B. A., Xiong, Y. Q., Melancon, B. J., Tomasiak, T. M., Ward, N. J., Yankovskaya, V., Oliver, K. M., Cecchini, G., Sulikowski, G. A., Tyska, M. J., Sullam, P. M., and Iverson, T. M. (2011) A structural model for binding of the serine-rich repeat adhesin GspB to host carbohydrate receptors, PLoS pathogens 7 , e1002112. - 46.
Siboo, I. R., Chambers, H. F., and Sullam, P. M. (2005) Role of SraP, a Serine-Rich Surface Protein of Staphylococcus aureus, in binding to human platelets, Infection and immunity 73 , 2273-2280. - 47.
O'Seaghdha, M., van Schooten, C. J., Kerrigan, S. W., Emsley, J., Silverman, G. J., Cox, D., Lenting, P. J., and Foster, T. J. (2006) Staphylococcus aureus protein A binding to von Willebrand factor A1 domain is mediated by conserved IgG binding regions, The FEBS journal 273 , 4831-4841. - 48.
Corcoran, P. A., Atherton, J. C., Kerrigan, S. W., Wadstrom, T., Murray, F. E., Peek, R. M., Fitzgerald, D. J., Cox, D. M., and Byrne, M. F. (2007) The effect of different strains of Helicobacter pylori on platelet aggregation, Canadian journal of gastroenterology = Journal canadien de gastroenterologie 21 , 367-370. - 49.
Arciola, C. R., Campoccia, D., Gamberini, S., Donati, M. E., and Montanaro, L. (2004) Presence of fibrinogen-binding adhesin gene in Staphylococcus epidermidis isolates from central venous catheters-associated and orthopaedic implant-associated infections, Biomaterials 25 , 4825-4829. - 50.
Brennan, M. P., Loughman, A., Devocelle, M., Arasu, S., Chubb, A. J., Foster, T. J., and Cox, D. (2009) Elucidating the role of Staphylococcus epidermidis serine-aspartate repeat protein G in platelet activation, Journal of thrombosis and haemostasis : JTH 7 , 1364-1372. - 51.
Miajlovic, H., Zapotoczna, M., Geoghegan, J. A., Kerrigan, S. W., Speziale, P., and Foster, T. J. (2010) Direct interaction of iron-regulated surface determinant IsdB of Staphylococcus aureus with the GPIIb/IIIa receptor on platelets, Microbiology 156 , 920-928. - 52.
Petersen, H. J., Keane, C., Jenkinson, H. F., Vickerman, M. M., Jesionowski, A., Waterhouse, J. C., Cox, D., and Kerrigan, S. W. (2010) Human platelets recognize a novel surface protein, PadA, on Streptococcus gordonii through a unique interaction involving fibrinogen receptor GPIIbIIIa, Infection and immunity 78 , 413-422. - 53.
Keane, C., Petersen, H., Reynolds, K., Newman, D. K., Cox, D., Jenkinson, H. F., Newman, P. J., and Kerrigan, S. W. (2010) Mechanism of outside-in {alpha}IIb{beta}3-mediated activation of human platelets by the colonizing Bacterium, Streptococcus gordonii, Arteriosclerosis, thrombosis, and vascular biology 30 , 2408-2415. - 54.
Keane, C., Petersen, H. J., Tilley, D. O., Haworth, J., Cox, D., Jenkinson, H. F., and Kerrigan, S. W. (2013) Multiple sites on Streptococcus gordonii surface protein PadA bind to platelet GPIIbIIIa, Thrombosis and haemostasis 110 , 1278-1287. - 55.
McDevitt, D., Francois, P., Vaudaux, P., and Foster, T. J. (1995) Identification of the ligand-binding domain of the surface-located fibrinogen receptor (clumping factor) of Staphylococcus aureus, Molecular microbiology 16 , 895-907. - 56.
McDevitt, D., Nanavaty, T., House-Pompeo, K., Bell, E., Turner, N., McIntire, L., Foster, T., and Hook, M. (1997) Characterization of the interaction between the Staphylococcus aureus clumping factor (ClfA) and fibrinogen, European journal of biochemistry / FEBS 247 , 416-424. - 57.
Walsh, E. J., Miajlovic, H., Gorkun, O. V., and Foster, T. J. (2008) Identification of the Staphylococcus aureus MSCRAMM clumping factor B (ClfB) binding site in the alphaC-domain of human fibrinogen, Microbiology 154 , 550-558. - 58.
Wann, E. R., Gurusiddappa, S., and Hook, M. (2000) The fibronectin-binding MSCRAMM FnbpA of Staphylococcus aureus is a bifunctional protein that also binds to fibrinogen, The Journal of biological chemistry 275 , 13863-13871. - 59.
Davis, S. L., Gurusiddappa, S., McCrea, K. W., Perkins, S., and Hook, M. (2001) SdrG, a fibrinogen-binding bacterial adhesin of the microbial surface components recognizing adhesive matrix molecules subfamily from Staphylococcus epidermidis, targets the thrombin cleavage site in the Bbeta chain, The Journal of biological chemistry 276 , 27799-27805. - 60.
Hartford, O., O'Brien, L., Schofield, K., Wells, J., and Foster, T. J. (2001) The Fbe (SdrG) protein of Staphylococcus epidermidis HB promotes bacterial adherence to fibrinogen, Microbiology 147 , 2545-2552. - 61.
Cunningham, M. W. (2000) Pathogenesis of group A streptococcal infections, Clinical microbiology reviews 13 , 470-511. - 62.
Carlsson, F., Sandin, C., and Lindahl, G. (2005) Human fibrinogen bound to Streptococcus pyogenes M protein inhibits complement deposition via the classical pathway, Molecular microbiology 56 , 28-39. - 63.
Shannon, O., Hertzen, E., Norrby-Teglund, A., Morgelin, M., Sjobring, U., and Bjorck, L. (2007) Severe streptococcal infection is associated with M protein-induced platelet activation and thrombus formation, Molecular microbiology 65 , 1147-1157. - 64.
Pietrocola, G., Schubert, A., Visai, L., Torti, M., Fitzgerald, J. R., Foster, T. J., Reinscheid, D. J., and Speziale, P. (2005) FbsA, a fibrinogen-binding protein from Streptococcus agalactiae, mediates platelet aggregation, Blood 105 , 1052-1059. - 65.
Schubert, A., Zakikhany, K., Schreiner, M., Frank, R., Spellerberg, B., Eikmanns, B. J., and Reinscheid, D. J. (2002) A fibrinogen receptor from group B Streptococcus interacts with fibrinogen by repetitive units with novel ligand binding sites, Molecular microbiology 46 , 557-569. - 66.
Kerrigan, S. W., Clarke, N., Loughman, A., Meade, G., Foster, T. J., and Cox, D. (2008) Molecular basis for Staphylococcus aureus-mediated platelet aggregate formation under arterial shear in vitro, Arteriosclerosis, thrombosis, and vascular biology 28 , 335-340. - 67.
Keane, C., Tilley, D., Cunningham, A., Smolenski, A., Kadioglu, A., Cox, D., Jenkinson, H. F., and Kerrigan, S. W. (2010) Invasive Streptococcus pneumoniae trigger platelet activation via Toll-like receptor 2, Journal of thrombosis and haemostasis : JTH 8 , 2757-2765. - 68.
Tilley, D. O., Arman, M., Smolenski, A., Cox, D., O'Donnell, J. S., Douglas, C. W., Watson, S. P., and Kerrigan, S. W. (2013) Glycoprotein Ibalpha and FcgammaRIIa play key roles in platelet activation by the colonizing bacterium, Streptococcus oralis, Journal of thrombosis and haemostasis : JTH 11 , 941-950. - 69.
Arman, M., Krauel, K., Tilley, D. O., Weber, C., Cox, D., Greinacher, A., Kerrigan, S. W., and Watson, S. P. (2014) Amplification of bacteria-induced platelet activation is triggered by FcgammaRIIA, integrin alphaIIbbeta3, and platelet factor 4, Blood 123 , 3166-3174. - 70.
Svensson, L., Baumgarten, M., Morgelin, M., and Shannon, O. (2014) Platelet Activation by Streptococcus pyogenes Leads to Entrapment in Platelet Aggregates, from Which Bacteria Subsequently Escape, Infection and immunity 82 , 4307-4314. - 71.
Sullam, P. M., Hyun, W. C., Szollosi, J., Dong, J., Foss, W. M., and Lopez, J. A. (1998) Physical proximity and functional interplay of the glycoprotein Ib-IX-V complex and the Fc receptor FcgammaRIIA on the platelet plasma membrane, The Journal of biological chemistry 273 , 5331-5336. - 72.
Miajlovic, H., Loughman, A., Brennan, M., Cox, D., and Foster, T. J. (2007) Both complement- and fibrinogen-dependent mechanisms contribute to platelet aggregation mediated by Staphylococcus aureus clumping factor B, Infection and immunity 75 , 3335-3343. - 73.
Naito, M., Sakai, E., Shi, Y., Ideguchi, H., Shoji, M., Ohara, N., Yamamoto, K., and Nakayama, K. (2006) Porphyromonas gingivalis-induced platelet aggregation in plasma depends on Hgp44 adhesin but not Rgp proteinase, Molecular microbiology 59 , 152-167. - 74.
Peerschke, E. I., Murphy, T. K., and Ghebrehiwet, B. (2003) Activation-dependent surface expression of gC1qR/p33 on human blood platelets, Thrombosis and haemostasis 89 , 331-339. - 75.
Nguyen, T., Ghebrehiwet, B., and Peerschke, E. I. (2000) Staphylococcus aureus protein A recognizes platelet gC1qR/p33: a novel mechanism for staphylococcal interactions with platelets, Infection and immunity 68 , 2061-2068. - 76.
Sarma, J. V., and Ward, P. A. (2011) The complement system, Cell and tissue research 343 , 227-235. - 77.
Ford, I., Douglas, C. W., Preston, F. E., Lawless, A., and Hampton, K. K. (1993) Mechanisms of platelet aggregation by Streptococcus sanguis, a causative organism in infective endocarditis, British journal of haematology 84 , 95-100. - 78.
Jackson, S. P., Yap, C. L., and Anderson, K. E. (2004) Phosphoinositide 3-kinases and the regulation of platelet function, Biochemical Society transactions 32 , 387-392. - 79.
Blair, P., Rex, S., Vitseva, O., Beaulieu, L., Tanriverdi, K., Chakrabarti, S., Hayashi, C., Genco, C. A., Iafrati, M., and Freedman, J. E. (2009) Stimulation of Toll-like receptor 2 in human platelets induces a thromboinflammatory response through activation of phosphoinositide 3-kinase, Circulation research 104 , 346-354. - 80.
Beutler, B., Hoebe, K., Du, X., and Ulevitch, R. J. (2003) How we detect microbes and respond to them: the Toll-like receptors and their transducers, J Leukoc Biol 74 , 479-485. - 81.
Stahl, A. L., Svensson, M., Morgelin, M., Svanborg, C., Tarr, P. I., Mooney, J. C., Watkins, S. L., Johnson, R., and Karpman, D. (2006) Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome, Blood 108 , 167-176. - 82.
Cognasse, F., Hamzeh-Cognasse, H., Lafarge, S., Delezay, O., Pozzetto, B., McNicol, A., and Garraud, O. (2008) Toll-like receptor 4 ligand can differentially modulate the release of cytokines by human platelets, Br J Haematol 141 , 84-91. - 83.
Scott, T., and Owens, M. D. (2008) Thrombocytes respond to lipopolysaccharide through Toll-like receptor-4, and MAP kinase and NF-kappaB pathways leading to expression of interleukin-6 and cyclooxygenase-2 with production of prostaglandin E2, Mol Immunol 45 , 1001-1008. - 84.
Clark, S. R., Ma, A. C., Tavener, S. A., McDonald, B., Goodarzi, Z., Kelly, M. M., Patel, K. D., Chakrabarti, S., McAvoy, E., Sinclair, G. D., Keys, E. M., Allen-Vercoe, E., Devinney, R., Doig, C. J., Green, F. H., and Kubes, P. (2007) Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood, Nat Med 13 , 463-469. - 85.
Beachey, E. H., Chiang, T. M., Ofek, I., and Kang, A. H. (1977) Interaction of lipoteichoic acid of group A streptococci with human platelets, Infect Immun 16 , 649-654. - 86.
Chugh, T. D., Burns, G. J., Shuhaiber, H. J., and Bahr, G. M. (1990) Adherence of Staphylococcus epidermidis to fibrin-platelet clots in vitro mediated by lipoteichoic acid, Infect Immun 58 , 315-319. - 87.
Sheu, J. R., Lee, C. R., Lin, C. H., Hsiao, G., Ko, W. C., Chen, Y. C., and Yen, M. H. (2000) Mechanisms involved in the antiplatelet activity of Staphylococcus aureus lipoteichoic acid in human platelets, Thromb Haemost 83 , 777-784. - 88.
Sheu, J. R., Hsiao, G., Lee, C., Chang, W., Lee, L. W., Su, C. H., and Lin, C. H. (2000) Antiplatelet activity of Staphylococcus aureus lipoteichoic acid is mediated through a cyclic AMP pathway, Thromb Res 99 , 249-258. - 89.
Lourbakos, A., Potempa, J., Travis, J., D'Andrea, M. R., Andrade-Gordon, P., Santulli, R., Mackie, E. J., and Pike, R. N. (2001) Arginine-specific protease from Porphyromonas gingivalis activates protease-activated receptors on human oral epithelial cells and induces interleukin-6 secretion, Infect Immun 69 , 5121-5130. - 90.
Rose, P. E., Armour, J. A., Williams, C. E., and Hill, F. G. (1985) Verotoxin and neuraminidase induced platelet aggregating activity in plasma: their possible role in the pathogenesis of the haemolytic uraemic syndrome, J Clin Pathol 38 , 438-441. - 91.
Bhakdi, S., Muhly, M., Mannhardt, U., Hugo, F., Klapettek, K., Mueller-Eckhardt, C., and Roka, L. (1988) Staphylococcal alpha toxin promotes blood coagulation via attack on human platelets, J Exp Med 168 , 527-542. - 92.
Arvand, M., Bhakdi, S., Dahlback, B., and Preissner, K. T. (1990) Staphylococcus aureus alpha-toxin attack on human platelets promotes assembly of the prothrombinase complex, J Biol Chem 265 , 14377-14381. - 93.
Ramsland, P. A., Farrugia, W., Bradford, T. M., Sardjono, C. T., Esparon, S., Trist, H. M., Powell, M. S., Tan, P. S., Cendron, A. C., Wines, B. D., Scott, A. M., and Hogarth, P. M. (2011) Structural basis for Fc gammaRIIa recognition of human IgG and formation of inflammatory signaling complexes, Journal of immunology 187 , 3208-3217. - 94.
Plummer, C., Wu, H., Kerrigan, S. W., Meade, G., Cox, D., and Ian Douglas, C. W. (2005) A serine-rich glycoprotein of Streptococcus sanguis mediates adhesion to platelets via GPIb, British journal of haematology 129, 101-109. - 95.
Sjobring, U., Ringdahl, U., and Ruggeri, Z. M. (2002) Induction of platelet thrombi by bacteria and antibodies, Blood 100, 4470-4477.