Enhanced vascular permeability and haemorrhage-inducing activity of zymosan-activated plasma

The intradermal injection into rabbits of various phagocytosible materials is known to induce polymorphonuclear leucocyte infiltration, protein exudation and microvascular haemorrhage. The injection of rabbit plasma, in which complement is activated with zymosan, also induces polymorphonuclear leucocyte infiltration. We investigated the effect of this soluble, non-ingestible stimulus to polymorphonuclear leucocyte accumulation on vascular integrity. Vascular permeability, measured with ¹²⁵I-human serum albumin, was markedly but only transiently increased 1 hr after zymosan-activated plasma injection. In contrast, haemorrhage or red blood cell extravasation, measured with ⁵⁹Fe-labelled red cells, developed only 4 hr after zymosan-activated plasma injection and continued for at least 10 hr. A direct correlation was found between the number of infiltrating polymorphonuclear leucocytes as measured with ⁵¹Cr-labelled leucocytes, and the degree of haemorrhage. Histological sections confirmed these changes. Plasma that was heat-inactivated (56°C, 30 min) or made functionally C5-deficient prior to zymosan activation, failed to induce haemorrhage and caused no, or only mild, leucocyte infiltration. It is postulated that the C5a(des arg) in zymosan-activated plasma not only induces polymorphonuclear leucocyte infiltration but also, directly or indirectly, causes microvascular damage.