Substance P receptor-mediated chemotaxis of human monocytes

The undecapeptide substance P (SP) was tested for its ability to promote human monocyte chemotaxis in a modified Boyden chamber assay. Substance P was found to be active in this assay system with an ED50 for chemotactic effect of approximately 10(-13) M. This response was shown to be chemotactic in nature since a concentration gradient of attractant was required for maximal effect. Other substance P analogs tested showed a rank order of potency of substance P greater than or equal to SP(3-11) greater than SP(8-11) approximately equal to SP(9-11) much greater than SP(1-9), SP, free acid. These results suggest that chemotactic responsiveness is largely encoded in the C-terminus of the molecule. The relative potency order for SP and its analogs in promoting monocyte chemotaxis correlates well with their potencies in displacing labeled SP when binding sites are directly measured in other tissues, such as rat brain or human lymphocytes. Additionally, the chemotactic effects of SP could be partially reversed by the weak antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP. The N-formyl peptide receptor antagonist, t-Boc-Phe-Leu-Phe-Leu-Phe, did not block SP-mediated chemotaxis, further indicating the specificity of these effects. These results suggest the existence of a specific substance P receptor on human monocytes which directs this chemotactic response. The ability of monocytes to respond chemotactically to SP may be relevant to the enhancing effects of SP in arthritis or other inflammatory diseases.