Differential chemotactic activities of sensory neuropeptides for human peripheral blood mononuclear cells.

Abstract

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, vasoactive intestinal peptide, and SP were chemotactic for PBL. Secretoneurin, known to induce monocyte chemotaxis, was unable to affect lymphocyte migration. Effects of SP on PBL were characterized by checkerboard analyses and represented true chemotaxis. Both T and B cells responded chemotactically to SP, the functional activity of SP residing in its C-terminal amino acid sequence. Involvement of neurokinin (NK) receptors was supported by inhibition of SP-induced migration of PBL with an NK1 receptor antagonist and induction of migration with [Sar9, Met(O2)11]SP and [PyrGlu6, Pro9]SP(6-11), two specific agonists for NK1 receptors, but not with [beta-Ala8]NK A(4-10), an agonist for NK2 receptors. PBL chemotaxis to SP was abolished by inhibition of tyrosin kinase but not by that of protein kinase C. Preincubation of PBL with pertussis or cholera toxin inhibited SP chemotaxis, indicating that in PBL, NK receptors for chemotaxis probably are coupled with G protein and involve a tyrosin kinase signaling pathway. We conclude that, together with calcitonin gene-related peptide and vasoactive intestinal peptide, SP is a lymphocyte chemoattractant, whereas secretoneurin, which is coreleased from sensory nerve endings, is not.

Chronic neurokinin-1 receptor antagonism fails to ameliorate clinical signs, airway hyper-responsiveness or airway eosinophilia in an experimental model of feline asthma

“…Finally, the perpetuation of airway inflammation is dependent on multiple redundant pathways and it has been speculated that following the establishment of a persistent cell-mediated inflammatory response, blockade of tissue NK-1 receptors is insufficient to prevent further eosinophil influx and airway remodeling. 3,33,34…”

Evidence for an association between an enhanced reactivity of interleukin-6 levels and reduced glucocorticoid sensitivity in patients with fibromyalgia

“…In more detail, muscle-derived IL-6 may elevate circulating IL-6 levels by the demonstrated potency of this cytokine to sensitize muscle nociceptors through induction of prostaglandin (PG)E 2 synthesis (Lahiri et al, 2001). Sensitized muscle nociceptors release the monocyte attractant neuropeptide substance P (SP) which has been shown in vitro to be able to increase circulating IL-6 levels by binding to a non-neurokinin SP receptor on monocytes (Kavelaars et al, 1994;Schratzberger et al, 1997;Mense, 2003).…”