MECHANISM OF FIBRONECTIN ENHANCEMENT OF GROUP-B STREPTOCOCCAL PHAGOCYTOSIS BY HUMAN NEUTROPHILS AND CULTURE-DERIVED MACROPHAGES

In previous studies, we reported that fibronectin (FN) markedly enhanc es phagocytic uptake of antibody-coated group B streptococci (GBS) by human polymorphonuclear leukocytes. Furthermore, administration of FN along with a GBS type-specific monoclonal or polyclonal antibody to in fected neonatal rats significantly enhances survival. In this study, w e have examined the molecular mechanism of this enhancement through ph agocyte receptors which recognize the Arg-Gly-Asp (RGD) peptide sequen ces contained within the FN molecule. Incubation of human polymorphonu clear leukocytes or culture-derived macrophages on coverslips coated w ith GRGDSP but not GRGESP markedly enhanced uptake of immunoglobulin G -coated GBS. The enhancing effect of the RGD-containing peptides was b locked by monoclonal antibodies B6H12 (directed against the integrin-a ssociated protein) and 7G2 (directed against the beta3-integrin recept or for RGD). These data suggest that FN enhancement of antibody-coated GBS uptake is mediated by the critical RGD sequence. Furthermore, thi s active peptide sequence may have an important role in immunotherapy of bacterial infections, especially in patients with decreased plasma FN concentrations.