Enhancement of vascular permeability upon serratial infection: activation of Hageman factor--kallikrein--kinin cascade.
A zinc dependent serratial 56K protease caused enhancement of vascular permeability followed by edema formation when injected into the guinea pig peripheral cornea, the subconjunctival space, or the skin. Because this enhancement was not affected by antihistamine, involvement of the kinin-generating system in this permeability enhancement was investigated. The 56K protease induced permeability much greater extent than that by bradykinin on weight basis, and more so on molar basis. The phenomenon was inhibited by soybean trypsin inhibitor, a well known inhibitor of plasma kallikrein, and also by corn trypsin inhibitor, which is the best inhibitor of the activated Hageman factor. In vitro experiments using numbers of synthetic peptide substrates, the 56K protease exhibited a similar substrate specificity to that of plasma kallikrein. Kallikrein is a known endogenous activator of Hageman factor. The enhancement by 56K protease was greatly augmented by inhibition of kininase II with Glu-Trp-Arg-Pro-Gln-Ile-Pro-Pro-OH (SQ 20,881), suggesting generation of bradykinin. Thus, these results indicate that the enhancement of vascular permeability induced by the 56K protease is caused by an activation of Hageman factor by 56K protease followed by subsequent activation of cascade amplification, and resulted in kinin generation in vivo.
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000503:physiopathology; D010450:Endopeptidases / Q000378:metabolism / Q000494:pharmacology*; D005174:Factor XII / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007610:Kallikreins / Q000502:physiology*; D007705:Kinins / Q000502:physiology*; D008297:Male; D008666:Metalloendopeptidases; D013379:Substrate Specificity
D006634:Histamine H1 Antagonists; D007705:Kinins; D006632:Histamine; D005174:Factor XII; D010450:Endopeptidases; D007610:Kallikreins; D008666:Metalloendopeptidases; C044194:microbial metalloproteinases; D001920:Bradykinin