Fibrinogen-derived peptide B beta 1-42 is a multidomained neutrophil chemoattractant.
The formation and degradation of fibrin play a central role in hemostasis, but other activities have been associated with fibrin(ogen)-derived peptides, which suggests that products of fibrin(ogen) turnover may be involved in inflammation and wound healing. The present study was undertaken to determine whether the plasmic fibrinogen-derived peptide B beta 1-42 has effects on inflammatory cells and fibroblasts (FB). B beta 1-42 was found to be a potent chemotaxin for neutrophils (PMN) and FB, maximally stimulating PMN migration at 10(-9) mol/L peptide. Unlike the chemotactic factors f-Met-Leu-Phe and C5a, B beta 1-42 did not induce the release of lysosomal hydrolases and superoxide anion from PMN, nor did it stimulate directed movement of monocytes (MN). These features of B beta 1-42 resemble the properties of human fibrinopeptide B (hFpB), the 14-reside, thrombin-cleaveable fragment that constitutes the amino terminus of B beta 1-42, and suggested that the chemotactic effects of B beta 1-42 are mediated through its hFpB domain. Against this conclusion, however, were observations that (a) desensitization of PMN with 10(-7) mol/L hFpB ablated chemotaxis to hFpB without affecting chemotaxis to B beta 1-42; (b) antiserum to hFpB, which recognizes the B beta 1-14 sequence both free and bound to larger fragments of the B beta chain, blocked hFpB chemotactic activity but did not affect B beta 1-42-mediated chemotaxis; (c) desensitization of PMN with equimolar amounts of hFpB and beta 15-42 (10(-7) mol/L), the isolated carboxyterminal sequence of B beta 1-42 remaining after the removal of hFpB, completely inhibited B beta 1-42-mediated chemotaxis; and (d) beta 15-42 itself was chemotactic for PMN. These data indicate that PMN recognize several independent domains within the amino terminal region of the human fibrinogen B beta chain and that these biologic effects extend to mesenchymal cells.
Skogen
W F
WF
Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110.
Senior
R M
RM
Griffin
G L
GL
Wilner
G D
GD
D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003182:Complement C5 / Q000494:pharmacology; D015936:Complement C5a; D003599:Cytoskeleton / Q000187:drug effects; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000648:ultrastructure; D010446:Peptide Fragments
D002630:Chemotactic Factors; D003182:Complement C5; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C035285:fibrinogen Bbeta (1-42); D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a