CD11B CD18 MEDIATES THE NEUTROPHIL CHEMOTACTIC ACTIVITY OF FIBRIN DEGRADATION PRODUCT-D DOMAIN/

Coagulation and fibrinolysis universally accompany tissue injury and r epair. The accumulation of regionally generated fibrin degradation pro ducts (FDP) may modify the local inflammatory response. We have found FDP to be potent neutrophil chemotaxins. We separated plasmin FDP by c hromatofocusing and found chemotactic activity limited to fractions co ntaining the fibrinogen D domain (D-D dimer and D monomer). The bioact ivity of the D-D dimer did not require an intact cross link site as re moval of this sequence with puff adder venom or hypocalcemic plasmic d igestion did not decrease chemotaxis. Peptide inhibition studies confi rmed that the chemotactic region did not involve terminal gamma chain sequences or alpha chain RGD motifs. The internal gamma chain peptide KYGWTVFQKRLDGSV (Pi), known to bind CD11b/CD18, exhibited concentratio n dependent chemotactic activity. Similarly, monoclonal antibodies dir ected against CD11b/CD18 blocked PMN migration to FDP without similar inhibition of chemotaxis to IL-8 or LTB4. Thus, neutrophil chemotaxis to FDP is mediated by interactions between the fibrinogen D domain and CD11b/CD18.