Generation of anaphylatoxins through proteolytic processing of C3 and C5 by house dust mite protease.

BACKGROUND

The group 3 allergen of Dermatophagoides species (Der p 3 and Der f 3) has been identified as a 30 kd trypsin-like protease of the house dust mite. We previously showed that the 30 kd protease from Dermatophagoides farinae (Df-protease) could activate the bradykinin-generating cascade and exacerbate inflammatory reactions.

OBJECTIVE

The purpose of this study was to determine whether Df-protease could enzymatically generate anaphylatoxins from complement components C3 and C5.

METHODS

Df-protease was incubated with human serum C3 or C5 in a purified system, and the anaphylatoxin activity produced was assayed by measuring enhancement of vascular permeability and release of histamine from mast cells triggered by C3a and by assessing chemotaxis of polymorphonuclear cells caused by C5a. We also attempted to determine whether protease isolated from house dust could cause release of C5a from C5.

RESULTS

Df-protease showed strong activation of C3 and C5, producing C3a and C5a by proteolytic cleavage of the complements. An appreciable amount of Df-protease was recovered in the house dust extract, and the house dust protease caused C5a release from C5.

CONCLUSION

Df-protease activated the complement system to produce anaphylatoxins. Thus it is suggested that house dust mite proteases may contribute to the pathogenesis of allergic and inflammatory diseases caused by house dust allergens.