Permeability Enhancing And Chemotactic Activities Of Lower Molecular Weight Degradation Products Of Human Fibrinogen

Abstract

Fibrinogen degradation products were investigated for leukocyte chemotactic activity and enhancement of vascular permeability. Fragments X, Y, D and E, and non-dialysable lower molecular weight degradation products were fractionated from plasmin digests of human fibrinogen by gel filtration, zone electrophoresis and ion exchange chromatography. They were assayed for chemotactic activity for human granulocytes by the modified Boyden chamber and for vascular permeability increasing activity in rabbit skin injected intravenously with pontamine blue.Both activities increased progressively with plasmin digestion of fibrinogen. Molecular weights of the permeability increasing and chemotactic activity fractions were 25,000-15,000 and 25,000 respectively. Both fractions had much higher activities than the fragment X, Y, D and E. The low molecular weight break down product with chemotactic activity showed the highest activity in rabbit skin in vivo as well. Granulocytic infiltration was most prominent 6-12 hr after intradermal injection and apparent even at an intradermal dose of 0.5/μg. Permeability enhancement of the active fraction reached to its muximum level at 5-10 min and was dose-dependent. Electron microscopic observations of the small blood vessels in rabbit skin correlated an increased permeability with the formation of characteristic gaps between adjacent endothelial cells and their contraction. Carbon particles used as a tracer passed into the vascular walls through these intercellular gaps.These observations add more support for the hypothesis that lower molecular weight degradation products of fibrinogen may be influential in contributing to granulocytic infiltration and enhanced permeability in lesions associated with deposits of fibrin and/or fibrinogen.