DIFFERENTIAL CHEMOTACTIC ACTIVITIES OF SENSORY NEUROPEPTIDES FOR HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

We studied the chemotactic effects of calcitonin gene-related peptide, vasoactive intestinal peptide, substance P (SP), and secretoneurin on PBMC and PBL using micropore filter assays. All four peptides induced migration of PBMC, whereas only calcitonin gene-related peptide, vaso active intestinal peptide, and SP were chemotactic for PBL. Secretoneu rin, known to induce monocyte chemotaxis, was unable to affect lymphoc yte migration. Effects of SP on PBL were characterized by checkerboard analyses and represented true chemotaxis. Both T and B cells responde d chemotactically to SP, the functional activity of SP residing in its C-terminal amino acid sequence. Involvement of neurokinin (NK) recept ors was supported by inhibition of SP-induced migration of PBL with an NK1 receptor antagonist and induction of migration with [Sar(9), Met( O-2)(11)]SP and [PyrGlu(6), Pro(9)]SP(6-11), two specific agonists for NK1 receptors, but not with [beta-Ala(8)]NK A(4-10), an agonist for N K2 receptors. PBL chemotaxis to SP was abolished by inhibition of tyro sin kinase but not by that of protein kinase C. Preincubation of PBL w ith pertussis or cholera toxin inhibited SP chemotaxis, indicating tha t in PBL, NK receptors for chemotaxis probably are coupled with G prot ein and involve a tyrosin kinase signaling pathway. We conclude that, together with calcitonin gene-related peptide and vasoactive intestina l peptide, SP is a lymphocyte chemoattractant, whereas secretoneurin, which is coreleased from sensory nerve endings, is not.