Related Experiment Videos
Hageman factor dependent pathway in local vascular permeability enhancement
Advances in Experimental Medicine and Biology
|January 1, 1986
Summary
The kallikrein-kinin system, specifically plasma prekallikrein, plays a key role in increasing vascular permeability induced by activated Hageman factor (beta HFa) in guinea pigs. This finding clarifies the Hageman factor-kallikrein-kinin cascade in this species.
Area of Science:
- Biochemistry
- Physiology
- Immunology
Background:
- The kallikrein-kinin system is involved in various physiological processes, including inflammation and vascular permeability.
- Activated Hageman factor (beta HFa) is known to induce vascular permeability, but its precise mechanism involving the kallikrein-kinin system requires further elucidation.
Purpose of the Study:
- To investigate the involvement of the kallikrein-kinin system in vascular permeability changes induced by intradermal injection of guinea pig activated Hageman factor (beta HFa).
- To characterize the role of plasma prekallikrein in the beta HFa-induced permeability response.
Main Methods:
- In vitro kinin generation assays using guinea pig plasma incubated with beta HFa.
- In vivo vascular permeability experiments in guinea pigs using beta HFa injections, with simultaneous administration of inhibitors (soybean trypsin inhibitor, carboxypeptidase B) or antibodies against plasma prekallikrein.
- Assessment of kininase II inhibition using SQ 20,881 to evaluate the role of kinin degradation.
Main Results:
- Beta HFa induced dose-dependent kinin generation in guinea pig plasma, dependent on plasma prekallikrein.
- Intradermal injection of beta HFa significantly increased vascular permeability in guinea pigs.
- Inhibition of plasma kallikrein or depletion of plasma prekallikrein markedly reduced the beta HFa-induced permeability response (>90% and 5-fold attenuation, respectively).
- Inhibition of kinin degradation (kininase II) augmented the permeability response, while direct kinin destruction diminished it.
Conclusions:
- The Hageman factor-kallikrein-kinin cascade in guinea pigs is similar to that observed in humans and bovines.
- Plasma prekallikrein is essential for the vascular permeability response induced by activated Hageman factor in guinea pigs.
- The study confirms the participation of the kallikrein-kinin system in mediating beta HFa-induced vascular permeability.