Stimulation of the chemotactic migration of human fibroblasts by substance P.
Neuropeptides exert a variety of modulatory effects on inflammatory cellular responses. In order to investigate further activities of these cytokines on mechanisms in inflammatory processes, we determined the ability of substance P to promote human fibroblast chemotaxis. Cell migration was measured by two different assay types in modified Boyden chambers. Substance P was found to be a potent chemoattractant for human fibroblasts in vitro, eliciting a concentration-dependent migratory response. In further investigations we tested the chemoattractant potency of the fragments substance P-(1-4) and substance P-(3-11). As only the C-terminal analog promoted migratory responses, we suggest that the chemotactic responsiveness is largely encoded by the C-terminus of the neuropeptide, which is known to be active on neurokinin receptors. Involvement of neurokinin receptors of type 1 in the chemotactic response to substance P was indicated by fibroblast migration toward optimal concentration of a selective NK1 receptor agonist but not a NK2 receptor agonist. The observed ability of human fibroblasts to respond chemotactically to substance P elucidated another proinflammatory activity of this neuropeptide.
Kähler
C M
CM
Department of Internal Medicine, Faculty of Medicine, University of Innsbruck, Austria.
Sitte
B A
BA
Reinisch
N
N
Wiedermann
C J
CJ
D000595:Amino Acid Sequence; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D003101:Collodion; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D011076:Polycarboxylate Cement; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000166:cytology; D013373:Substance P / Q000494:pharmacology*
D011076:Polycarboxylate Cement; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C005506:polycarbonate; D013373:Substance P; D003101:Collodion