Mediation of increased vascular permeability after complement activation. Histamine-independent action of rabbit C5a.

Intradermal injection of zymosan into nonsensitized rabbits induces plasma exudation, which is dependent on two mediators: C5a generated in extravascular tissue fluid and a vasodilator prostaglandin generated from substrates localized in cell membranes. This relationship between the complement system and the prostaglandin synthesis system had not previously been explored, and complement activation has generally been associated with increased vascular permeability via histamine release. We report that C5a increases vascular permeability by a mechanism that is not dependent on histamine release; however plasma exudation is virtually undetectable in the absence of a vasodilator substance. Because the permeability-increasing activity is stable in plasma, analogy with other species suggests that the activity is a result of C5a devoid of its carboxyl terminal arginine (C5a des Arg). This relates the observed permeability-increasing activity with effects on leukocytes rather than effects as an anaphylatoxin.