PMID: 2480329Nov 1, 1989Paper

Activation of human neutrophils by substance P: effect on FMLP-stimulated oxidative and arachidonic acid metabolism and on antibody-dependent cell-mediated cytotoxicity.

Immunology
A WozniakR Scicchitano

Abstract

We show that the neuropeptide, substance P (SP), a putative mediator of neurogenic inflammation, is a potent regulator of mature, human neutrophil function. SP increased neutrophil cytotoxic activity against an antibody-coated target (P815 cells) in a dose-dependent manner. The maximal effect was noted at an SP concentration of 10(-4) M, when cytotoxicity increased from 4.7 +/- 0.9% to 33.4 +/- 10.3%. This effect was not due to toxicity of SP against the target cells and was antibody-dependent. The level of cytotoxic activity induced by SP was comparable to that described for a number of cytokines, such as GM-CSF, under identical assay conditions. SP-induced cytotoxicity was 73.1 +/- 5.8% of that produced by an optimum concentration of conditioned medium known to contain a number of cytokines which activate mature neutrophils. In addition, SP enhanced FMLP-stimulated superoxide anion production by neutrophils in a dose-dependent fashion. Neutrophils preincubated with medium or 7.5 x 10(-5) M SP and then stimulated with 10(-7) M FMLP produced 7.9 +/- 2.7 and 29.9 +/- 3.7 nmol superoxide anion/10(6) cells, respectively. This priming effect of SP was rapid in onset (less than 15 min) and was maximal from 15 to 60 min, after which ...Continue Reading

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