The directed migration of leukocytes into a site of inflammation is determined in part by a class of small molecular weight proteins called chemokines. In addition, extracellular matrix proteins also influence the behavior of leukocytes migrating into tissues via ligation of integrin receptors. Previous studies in our laboratory have demonstrated that cell-binding fragments of the extracellular matrix protein fibronectin inhibited the migration of human neutrophils to the neutrophil specific chemokine, Interleukin-8 (IL-8). We hypothesize that cell-binding fragments of fibronectin interact with integrin receptors on the neutrophil resulting in a desensitization of IL-8 receptors. We are investigating the mechanism of integrin receptor mediated desensitization of chemokine receptors by examining signal transduction of IL-8 receptors stably transfected in a cell line. The potential crosstalk between integrin and chemokine receptors is clearly important in furthering our understanding of the control of leukocyte migration and activation in chronic inflammatory responses.