EFFECTS OF NEUROPEPTIDES ON NEUTROPHIL MIGRATION THROUGH NONCELLULAR AND ENDOTHELIAL BARRIERS

Background: Neuropeptides and neutrophils are postulated to be important immune effector molecules and cells, respectively, in a variety of lung inflammatory conditions. Methods: We examined the effects of three lung neuropeptides, substance P vasoactive intestinal peptide (VIP), and somatostatin and two relatively protease-resistant peptides, helodermin and sandostatin, on human neutrophil migration across 3 mum pore filters and human endothelial monolayers cultured on these filters. Results: At concentrations of 1 to 10 mumol/L, substance P induced significant neutrophil migration that was dose-responsive and equivalent through endothelium and filters. Neither VIP, helodermin, somatostatin, nor sandostatin induced significant neutrophil migration through either barrier at doses of 10(-14) to 10(-5) mol/L. Because VIP and somatostatin have been reported to inhibit some inflammatory cell functions, we also examined their effects on chemoattractant-induced neutrophil migration. Pretreatment of neutrophils and/or endothelium with VIP or somatostatin at either 10(-5) or 10(-10) mol/L did not significantly inhibit formyl-methionyl-leucyl-phenylalanine-, leukotriene B4-, or platelet activating factor-induced neutrophil migration through naked filters or endothelium. Thus only substance P had significant effects on neutrophil chemotaxis. Conclusions: Substance P, but not VIP or somatostatin, may be important in directly influencing neutrophil migration across endothelium towards lung inflammatory sites. However, all three neuropeptides might still modulate neutrophil functions and lung inflammatory responses through effects on other lung cells.