ABSTRACT
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, MS 415, 800 Rose Street, Lexington, KY 40536-0084, USA
Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide present primarily in nociceptive nerve fibres in the peripheral nervous system. Similar to substance P, one of its major functions is as a mediator of neurogenic inflammation. It does this by regulating both vascular and cellular functions at local sites of inflammation and in lymphoid tissue. There are two isoforms of CGRP, a and (3, derived from two distinct genes, one of which also encodes the hormone calcitonin. A CGRP receptor has been recently described that requires the expression of the calcitonin receptor like receptor (CRLR) gene product as well as a member of the recently described receptor activity modulating protein (RAMP) family, RAMP 1. CGRP receptors have been identified in a number of tissues including the immune system. In the immune system, CGRP receptors have been identified on mature T and B cells and macrophages, and on developing B cells in the bone marrow. CGRP has a number of effects on lymphoid tissue, many of which are inhibitory in nature. It inhibits T cell proliferation, apparently by inhibition of IL-2 production. In macrophages, it inhibits Ag presentation and other macrophage functions including phagocytosis and the oxidative burst. It also stimulates production of a number of lymphokines including IL-6, IL-10 and TNF-α. During B cell development in the bone marrow it acts as a negative feedback inhibitor of B cell development. It does this directly by inhibiting the proliferative effect of IL-7 on early pro-B cells and indirectly by induction of inhibitory cytokines including IL-6 and TNF-α in bone marrow macrophages and other stromal cells. Overall, there is substantial experimental evidence demonstrating that CGRP can influence the function and development of inflammatory and immune cells in local microenvironments by specific receptor-mediated mechanisms.
