Hageman factor dependent pathway in local vascular permeability enhancement.

The possibility of an involvement of the kallikrein-kinin system in increasing vascular permeability induced by intradermal injection of the guinea pig activated Hageman factor (beta HFa) was examined. In vitro system, the kinin generation was observed in guinea pig plasma when the plasma was incubated with beta HFa. This kinin generation was dependent upon the dose of beta HFa added and upon the presence of plasma prekallikrein, since 97 percent of the kinin release was diminished by removing the prekallikrein in plasma by treatment with anti-prekallikrein antibody. These results suggested that the Hageman factor-kallikrein-kinin cascade in guinea pig was similar to those in human and bovine plasma. In the permeability experiment in vivo, a simultaneous injection of soybean trypsin inhibitor (10(-6) M), which is the inhibitor of guinea pig plasma kallikrein, inhibited the permeability response to beta HFa by more than 90 percent. The permeability response to beta HFa was attenuated 5 fold in animals depleted of the circulating plasma prekallikrein by intraarterial antibody administration. These results indicated the participation of plasma prekallikrein in the permeability reaction to beta HFa. A simultaneous injection of a kinin destructive enzyme, carboxypeptidase B, diminished the permeability reaction to beta HFa, without any inhibition of the amidolytic activity of beta HFa or plasma kallikrein. A simultaneous injection of an inhibitor of a kinin destructive enzyme (kininase II), SQ 20,881(Glu-Tyr-Pro-Arg-Pro-Gln-Ile-Pro-Pro-OH), augmented the permeability reaction to beta HFa 10 fold, without any effect on the amidolytic activity of beta HFa or plasma kallikrein.(ABSTRACT TRUNCATED AT 250 WORDS)