Neutrophils are involved in the increased vascular permeability produced by activated complement in man

To investigate the role of neutrophils in complement-induced changes in vascular permeability, skin wheal and flare responses to intradermal injection of autologous activated serum complement were measured in normal and neutropenic subjects. In normal subjects, responses were dose-dependent and were abolished by removal of C5 from serum. Biopsy of a wheal revealed neutrophils adherent to vascular endothelium. In neutropenic subjects (neutrophil count less than 0.5 X 10(9)/l), responses to complement-activated serum or a low molecular weight fraction from it were significantly reduced. This could not be accounted for by a reduction in concentration of C5 conversion products. In one subject with chronic granulomatous disease a normal response was produced. Local injection of the anti-histamine (H1) drug clemastine produced only partial inhibition of responses, while almost totally abolishing histamine-induced wheals. Systemic anti-inflammatory drugs had no effect. The data suggest that the microvascular response to activated complement in man is at least partly due to an interaction between C5 fragments and neutrophils.