SUBSTANCE-P (NEUROKININ-1) RECEPTOR IS A MARKER OF HUMAN MUCOSAL BUT NOT PERIPHERAL MONONUCLEAR-CELLS - MOLECULAR QUANTITATION AND LOCALIZATION

Reciprocal communication between the immune system and the neuroendocr ine system is mediated via a common chemical language of shared ligand s and receptors, The neuropeptide substance P (SP) has been implicated as a mediator of immunomodulation. The evidence for substance P recep tors on human lymphocytes is, however, controversial. The aims of the present study are to investigate substance P receptor (SPR) expression in human peripheral and mucosal mononuclear cells and to identify cel lular sites of expression in human colonic mucosa, Using reverse-trans criptase PCR, we demonstrate that PBMC isolations are negative for SPR mRNA expression, whereas lamina propria mononuclear cell (LPMC) isola tions express on average eight SPR mRNA transcripts per cell. In situ hybridization performed on surgically resected colonic tissue confirms the expression of SPR mRNA in LPMC in vivo. SPR mRNA signal was detec ted in LPMC, lymphoid follicles, and epithelium. The complementary tec hnique of immunohistochemistry gave a similar distribution of SPR expr ession that colocalized with CD45 immunoreactivity, Dual-fluorochrome flow cytometry revealed SPR expression by CD4, CD45RO, CD45RA, CD8, CD 19, and CD14 LPMC subsets, but not PBMC, Our findings suggest that SPR expression is distinctive of human colonic mucosal mononuclear cells and support a direct role for SP in mucosal immunomodulation.