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 microns 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.
Carolan
E J
EJ
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Casale
T B
TB
D002460:Cell Line; D002464:Cell Migration Inhibition; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009479:Neuropeptides / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology*; D015282:Octreotide / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D009479:Neuropeptides; D010455:Peptides; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; C040442:heliodermin; D015282:Octreotide