1. Introduction
An estimated 300 million people worldwide have asthma, and 250,000 deaths are attributed annually to the disease. From 2001 to 2009, the number of people diagnosed with asthma grew by 4.3 million. Allergic airway inflammation is closely related to airway hyperresponsiveness (AHR), the production of mucus, and airway remodeling. This inflammation is mediated by the T helper type 2 (Th2)-cell response, the upregulation of interleukins (IL)-4, 5, and 13, which are produced by activated CD4+ T cells, and by elevated immunoglobulin E (IgE) production. Asthma has long been associated with atopy, a predilection for producing antigen-specific IgE antibodies against environmental allergens capable of mediating hypersensitivity reactions, particularly immediate skin reactions [1, 2]. Many environmental proteases are believed to be allergens that elicit allergic airway inflammation. Allergens from house dust mites [3], cockroaches [4], fungi [3], and pollens have been reported to contain cysteine, serine, and aspartic proteases [5].
Recently, asthma patients with high serum IgE levels, but who do not react to known allergens in skin prick tests, have been identified, suggesting the presence of unknown environmental allergens [6]. We hypothesize that free living amoeba (FLA) are undiscovered aeroallergens. One of the FLA,
2. Acanthamoeba trophozoites elicited a strong allergic airway inflammation response
Airway allergens are experimentally confirmed by the ability to elicit allergic airway inflammation when it was inhaled. Ovalbumin (OVA) is one of commonly used the experimental allergens, but is unable to elicit allergic airway inflammation if directly administered by inhalation without any allergens. By contrast, pollens and fungal-derived allergens can easily elicit allergic responses when inhaled through the airway tract [17-19]. Therefore, if repeated administration of
It is possible for a person to come into contact with as many as 100 trophozoites at a time from
3. Acanthamoeba produced strong ES proteases that could induce severe allergic inflammation in airway through Protease Activated Receptor 2 (PAR2)
Proteases of
Park et al., introduced protease-containing ES protein samples of
Recently PARs is known as belong to seven-transmembrane domain G protein coupled receptors [26]. They are activated through proteolytic cleavage of their N-terminal “tethered ligand” domains [27]. PAR1, 2, 3 and PAR4 have been cloned. They can be activated by thrombin (PAR1, PAR3, and PAR4), also can be activated by neutrophil protease 3, mast cell tryptase, trypsin, and several serine proteases (PAR2) [28]. Park et al. treated ES proteins with serine protease inhibitor (PMSF) and evaluated airway inflammation. The results showed that Pre-treatment with PMSF lead to a significant decrease in most values of the inflammation index, relative to administration of untreated ES proteins. The airway hyperresistant response (AHR) to methacholine following ES protein administration was likewise decreased by PMSF pre-treatment [20]. In addition, the infiltration of immune cells was lower in the PMSF-treated group, compared with ES protein-treatment alone; most notably, the number of eosinophils significantly decreased. In evaluation of the airway allergic inflammation induced by
4. ES proteins activate dendritic cells (DCs) and the differentiation of Th2 cells
PARK et al., suggested that
Enhancement of IL-5, IL-4, IL-13, and CXCL1 (eotaxin) are critical for the induction of allergic asthma by Th2 cells [29, 30]. Furthermore, CCR3, CCR4, and CCR8 was expressed on Th2 cells. Imai et al., suggested that TARC, MDC, and high-affinity CCR4 ligands can induce Th2 cells migration to the selective sites [31]. Therefore, production of serine protease activity contained
5. Acanthamoeba antigens are detected in house dust, and significantly high level of anti Acanthamoeba IgE in asthma patients
Park et al., demonstrated that after samples of house dust were reacted with total serum from
6. Conclusion
Acknowledgments
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A2042979).
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