HUMAN POLYMORPHONUCLEAR LEUKOCYTES STORE LARGE AMOUNTS OF TERMINAL COMPLEMENT COMPONENTS C7 AND C6, WHICH MAY BE RELEASED ON STIMULATION

Secretion of the C factors C7, C6, and C3 by human polymorphonuclear l eukocytes (PMNs) and PBMCs was studied by ELISA and immunoblot. The re lease of C7 and C6 by PMNs during 24 h of culture was 16-fold and 6-fo ld higher, respectively, than the C3 release, with median concentratio ns of 50.2 ng/ml, 18.3 ng/ml, and 3.1 ng/ml, respectively. In PBMC cul tures, C release was considerably lower, and there was a different sec retory pattern with a 6-fold higher release of C3 compared with C7 and C6. Stimulation with PMA led to a more rapid and complete secretion o f the components to the culture media, whereas treatment with unopsoni zed Candida species did not affect the release. PMN release of C facto rs was not dependent on protein biosynthesis, and there was no indicat ion of a selective uptake of C7 from serum as demonstrated by incubati ng PMNs from a subject with allotype C7 N in C7 M serum. Thus, the C c omponents were probably produced by the PMNs or their bone marrow prec ursors before ex vivo culture. In cell lysates of freshly isolated cel ls, median C7, CG, and C3 contents of 1 x 10(7) PMNs were 149.7, 60.1, and 10.4 ng/ml, respectively, whereas the corresponding values for 1 x 10(7) PBMCs were 3.2, 2.6, and 14.6 ng/ml, respectively. The C6 and C7 were shown to incorporate into the terminal complement complex, and their molecular integrity was supported by identical m.w, to C6 and C 7 present in normal serum. PMNs may represent a major source of C7 and C6 and may be more important than monocytes or macrophages in contrib uting terminal C components at a site of inflammation. This suggests a new role for the PMN as a C membrane attack modulator.