Modulation of polymorphonuclear leukocyte microbicidal activity and oxidative metabolism by fibrinogen degradation products D and E.
Fibrinogen degradation products (FDP) D and E are typically present 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 micrograms/ml FDP did not affect phagocytosis, but reduced by greater than 90% the cells' ability to inhibit bacterial colony growth compared with control PMN incubated with albumin or fibrinogen. FDP (10-100 micrograms/ml) inhibited PMN O2- release and chemotaxis stimulated by FMLP by 17-50% (P less than 0.005) and 41% (P less than 0.01), respectively. Fragment E3, and not fragment D1, was primarily responsible for inhibition of FMLP-induced PMN O2- 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 O2- 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 micrograms/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.
Kazura
J W
JW
Department of Medicine, University Hospitals of Cleveland, OH 44106.
Wenger
J D
JD
Salata
R A
RA
Budzynski
A Z
AZ
Goldsmith
G H
GH
D000328:Adult; D001095:Arachidonic Acids / Q000378:metabolism; D001770:Blood Bactericidal Activity; D001779:Blood Coagulation Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D004789:Enzyme Activation; D005338:Fibrin Fibrinogen Degradation Products / Q000502:physiology*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology / Q000502:physiology*; D010101:Oxygen Consumption; D010587:Phagocytosis; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
D001095:Arachidonic Acids; D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; C018543:fibrinogen fragment E; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate