title: Fibrinogen is degraded and internalized during incubation with neutrophils, and fibrinogen products localize to electron lucent vesicles.
abstract: A biologically relevant relationship exists between neutrophils and coagulation processes. Several studies have focused on the ability of neutrophil proteases (both intracellular and membrane-associated) to degrade fibrinogen. The present study investigates the events following the interaction of activated neutrophils with soluble fibrinogen. During incubation of PMA-stimulated neutrophils with fibrinogen at 37 degrees C, fibrinogenolysis occurred, and degraded fibrinogen became associated with the neutrophil. Immunoelectron microscopy identified these fibrinogen products to be located within electron lucent vesicles, and not on the surface of the cell, suggesting that they are internalized. Although a specific interaction between fibrinogen and the neutrophil membrane might assist uptake, in the presence of physiological concentrations of fibrinogen, internalization occurred largely via a non-specific pinocytic process. Studies at low temperature revealed that both intact and degraded forms of fibrinogen can associate with neutrophils. The fibrinogen products detected intracellularly in experiments performed at 37 degrees C might represent uptake of degraded as well as intact forms of fibrinogen, the latter being rapidly degraded intracellularly. This route of fibrinogenolysis contributes minimally to the overall extent of the degradation process, the majority occurring extracellularly. Neutrophils thus possess a proteolytic mechanism for preventing accumulation of surface ligand, perhaps allowing them to evade the immunomodulatory effects of such ligands during inflammation.
authors.affiliation: MRC/UCT Liver Research Centre, Department of Medicine, University of Cape Town, Observatory, Cape Town, 7925, South Africa.
authors.forename: Richard
authors.initials: R
authors.lastname: Kirsch
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Jaffer
authors.forename: Vivienne E
authors.initials: VE
authors.lastname: Woodburne
authors.forename: Trevor
authors.initials: T
authors.lastname: Sewell
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Kelly
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Kirsch
authors.forename: Enid G
authors.initials: EG
authors.lastname: Shephard
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008854:Microscopy, Electron; D009504:Neutrophils / Q000378:metabolism* / Q000648:ultrastructure; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D005340:Fibrinogen; D013755:Tetradecanoylphorbol Acetate