Substance P: a neurogenic mediator of acute cellular inflammation in the dog?
Substance P (SP) is a neuropeptide that has recently been implicated in the pathogenesis of neurogenic inflammation. SP has been shown to activate polymorphonuclear leukocytes (PMN) as well as other inflammatory cells. The present study investigated the direct stimulatory and priming effects of SP on canine PMN aggregation and migration. Direct stimulation of cell migration by SP was present at an unphysiologically high concentration of the mediator. However, when micromolar concentrations of SP were added to PMN prior to stimulation with sub-optimal concentrations of leukotriene B4 (LTB4), the cells exhibited enhanced aggregation and migration, i.e. priming, when stimulated with the latter. Since SP has been reported to act via the formyl-Met-Leu-Phe (fMLP) chemotaxin receptor, this mediator was also studied and found not to possess any effects similar to SP. Thus, the results indicate that SP acts as a primer of canine PMN functions in vitro via a receptor different from that for fMLP. Before ascribing SP a mediator role in canine neurogenic inflammation, in vivo studies determining the concentrations of, and responses to SP in inflamed tissue should be performed.
Thomsen
M K
MK
Department of Pharmacology, Leo Pharmaceutical Products, Ballerup, Denmark.
D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004285:Dogs / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000209:etiology*; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology*
D007975:Leukotriene B4; D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine