Abstract
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.
