Fibrinogen-derived peptide B beta 1-42 is a multidomained neutrophil chemoattractant

• Published in: Blood 1988-05, Vol.71 (5), p.1475-1479
• Main Authors: Skogen, W F, Senior, R M, Griffin, G L, Wilner, G D
• Format: Article
• Language: English
• Subjects: Chemotactic Factors - pharmacology; Chemotaxis, Leukocyte - drug effects; Complement C5 - pharmacology; Complement C5a; Cytoskeleton - drug effects; Fibrin Fibrinogen Degradation Products - pharmacology; Fibroblasts - drug effects; Humans; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils - drug effects; Neutrophils - ultrastructure; Peptide Fragments
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V71.5.1475.1475

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.