Modulation of polymorphonuclear leukocyte microbicidal activity and oxidative metabolism by fibrinogen degradation products D and E

Abstract

Fibrinogen degradation products (FDP) D and E are typically preent in blood of patients with disseminated intravascular coagulation and related conditions in which granulocyte (PMN) defense against bacterial infection may be compromised. This study was intended to determine whether FDP modify PMN functions critical to their bactericidal activity. Incubation of human PMN and Escherichia coli with 50-100 μg/ml FDP did not affect phagocytosis, but reduced >90% the cells' ability to inhibit bacterial colony growth compared with control PMN incubated with albumin or fibrinogen. FDP (10-100 μg/ml) inhibited PMN O(2̄) release and chemotaxis stimulated by FMLP by 17-50% (P < 0.005) and 41% (P < 0.01), respectively. Fragment E3, and not fragment D1, was primarily responsible for inhibition of FMLP-induced PMN O(2̄) release. Phorbol myristate acetate (10 ng/ml), 1-oleoyl-2-acetylglycerol (10-6 M), AA (4.2 x 10-5 M), and zymosan-activated serum-stimulated PMN O(2̄) release were also decreased 37-63% by FDP compared with control protein. There are at least two mechanisms by which FDP may impair PMN responses. With respect to FMLP, FDP (16-100 μg/ml) inhibited specific binding to the cell surface over a ligand concentration range of 1.4-85 nM [3H]FMLP. In contrast, FDP did not effect the extent of phorbol ester binding to PMN but blocked activation of protein kinase C. These data suggest that elevated plasma FDP inhibit several PMN functions critical to the bactericidal role of these inflammatory cells.