Substance P causes adhesion of neutrophils to endothelial cells via protein kinase C

The sensory neuropeptide substance P is known to be involved in neurogenic inflammation. We examined the effect of substance P on neutrophil adhesion to human umbilical vein endothelial cells (HUVEC). Stimulation of HUVEC with substance P increased their adhesion to neutrophils in a time- and concentration (10(-10)-10(-7) M)-dependent manner. The adhesion was inhibited by the tachykinin NK1 receptor antagonist (+)-(2S,3S)-3-(2-Methoxybenzylamino)-2-phenylpiperidine (CP-99,994) and also by the protein kinase C inhibitors 1-(5-Isoquinolinesulfonyl)-2-methyl piperazine (H-7) and bisindolylmaleimide (BIM), but not by the protein kinase A inhibitor N-12-(p-Bromocinnamylamino) ethyl]-S-isoquinoline sulfonamide (H-89). These results indicate that substance P induces adhesion of neutrophils to HUVEC by activation of protein kinase C via the NK1 receptor on the HUVEC.