Chemotactic response to human C3a and C5a anaphylatoxins. I. Evaluation of C3a and C5a leukotaxis in vitro and under stimulated in vivo conditions.

Abstract

Human C5a was maximally active over a narrow concentration range of 2 to 6 × 10-7 M as estimated in rabbits by utilizing a skin window assay technique (Otani and Hugli, 1977). Human C5ades Arg also stimulated neutrophil accumulation under simulated in vivo conditions but at a slightly higher concentration range of 0.2 to 1.2 × 10-6 M. The C5ades Arg did not require added serum to produce an apparent leukotactic response in vivo, but, as in vitro, activity was not observed at levels above or below the effective concentration ranges indicated for C5a and C5ades Arg C3a was inactive over a concentration range of 5.5 × 10-9 to 5.5 × 10-6 M as an attractant for rabbit neutrophils in the skin window assay. The concentrations of C5a or C5ades Arg that are required to induce chemotaxis under simulated in vivo conditions correspond to the potential serum levels of these factors (e.g., 4 to 5 × 10-7 M). It is suggested from our quantitative measurements that the predominant chemotactic activity generated in human serum during C activation is associated with the C5ades Arg molecule. Therefore, C5ades Arg exhibits the potential for playing a predominant functional role under physiologic conditions as a major humoral chemotactic factor.