Mechanism of substance P-induced activations of human neutrophils.

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To determine the mechanism by which substance P (SP) activates human neutrophils, we examined the potency of SP for inducing chemotaxis, lysozyme release, and increase in cytosolic free Ca2+ concentration ( [Ca2+] i) in human blood neutrohils. We also examined the effects of EGTA and of a formyl-Met-Leu-Phe (FMLP) antagonist on the responses. SP (10-6 to 10-4 M) induced chemotaxis, lysozyme release, and the increase in [Ca2+] i of the neutrophils dose-dependently. Preincubation with EGTA (10 mM) decreased the SP-induced increase in [Ca2+] i by 90%, whereas EGTA decreased the FMLP-induced increase in [Ca2+] i only by 37%, suggesting that the activations of human neutrophils by SP are dependent on the influx of extracellular Ca2+. An FMLP antagonist, boc-Phe-Leu-Phe-Leu-Phe, inhibited the FMLP-induced chemotaxis and increase in [Ca2+] i, but it did not inhibit the SP-induced respones. We suggest that SP induces the activations of human neutrophils by the different mechanism from that of FMLP.
日本炎症・再生医学会の論文