Alteration of chemoattractant receptor expression regulates human neutrophil chemotaxis in vivo.

OBJECTIVE: To elucidate the mechanisms that regulate human neutrophil delivery in vivo, as well as the mechanisms that lead to observed reduction in polymorphonuclear (PMN) delivery to remote sites in septic patients. METHODS: Alterations in human PMN chemoattractant receptor expression and chemotactic function in vivo were evaluated in two distinct experiments: exudate PMNs (PMNs that have undergone transmigration to skin window blisters in controls) and septic PMNs (circulating PMNs from septic patients in the intensive care unit) were both separately compared with control circulating PMNs. RESULTS: Exudate PMNs displayed increased C5a receptors and C5a chemotaxis, and reduced interleukin-8 receptors (both IL-8 RA and IL-8 RB) and IL-8 chemotaxis. Septic PMNs displayed reduced C5a and IL-8 receptors and decreased C5a chemotaxis but no change in IL-8 chemotaxis. IL-8 but not C5a receptor gene expression decreased in parallel to receptor alteration. CONCLUSIONS: These results suggest that change in PMN chemoattractant receptor expression serves to regulate PMN chemotaxis in vivo; that exudate PMN chemotaxis depends more on C5a than IL-8; and that diminished chemoattractant receptors and chemotaxis in septic PMNs may explain decreased PMN delivery in these patients.