Triggering of the vascular permeability reaction by activation of the Hageman factor-prekallikrein system by house dust mite proteinase.
A 30-kilodalton (kDa) proteinase from the house dust mite Dermatophagoides farinae (Df-proteinase) was recently purified (Takahashi et al. (1990) Int. Arch. Allergy Appl. Immunol. 91, 80-85). In this paper we detailed the biological activities of the Df-proteinase. The activation of the kinin cascade by Df-proteinase was examined in vitro by using purified guinea pig Hageman factor (HF), prekallikrein (PK) and high-molecular-weight kininogen (HMWK) and the effect of this proteinase on endogenous human plasma proteinase inhibitors (serpins) and alpha 2-macroglobulin was tested. In addition, enhancement of the vascular permeability reaction in guinea pig skin by Df-proteinase was examined in vivo. These experiments showed that Df-proteinase could activate all the steps of the kinin-generating cascade, i.e., HF, PK and HMWK, and that Df-proteinase retained proteolytic activity even in the presence of an excess amount of endogenous proteinase inhibitors in plasma. We also found that the marked enhancement of the vascular permeability reaction was induced by Df-proteinase via the activation of the kinin-generating cascade without the release of histamine. From these results, we conclude that the proteinase of the house dust mite, Df-proteinase, has the potential to generate bradykinin and that the presence of this proteinase in biological systems would exacerbate inflammatory reactions in some pathological conditions.
Maruo
K
K
Department of Microbiology, Kumamoto University Medical School, Japan.
Akaike
T
T
Matsumura
Y
Y
Kohmoto
S
S
Inada
Y
Y
Ono
T
T
Arao
T
T
Maeda
H
H
D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D002199:Capillary Permeability; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D005174:Factor XII / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D007704:Kininogens / Q000378:metabolism; D007705:Kinins / Q000378:metabolism; D008297:Male; D008925:Mites / Q000201:enzymology*; D011288:Prekallikrein / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism; D012867:Skin / Q000098:blood supply
D007704:Kininogens; D007705:Kinins; D011480:Protease Inhibitors; D005174:Factor XII; D011288:Prekallikrein; D010450:Endopeptidases; D001920:Bradykinin