Modulation of B Lymphocyte Differentiation by Calcitonin Gene-Related Peptide (CGRP)

McGillis, Joseph P.; Humphreys, S.C.; Rangnekar, Vivek M.; Ciallella, John R.

doi:10.1006/cimm.1993.1208

Cited by 35 publications

(6 citation statements)

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“…To determine whether the in vivo effect of CGRP on early B cell progenitors is specific, mice were treated with calcitonin as a nonspecific peptide control or with CGRP and the CGRP antagonist CGRP 8 -37 [31]. Calcitonin, derived from the same gene as CGRP, is of similar size and charge, has little sequence homology, and does not cross-react with lymphocyte CGRP receptors [9,10,32]. CGRP 8 -37 is a truncated form of CGRP lacking the first 7 amino acids that acts as an antagonist at CGRP receptors.…”

Section: Resultsmentioning

confidence: 99%

“…In vitro studies with cell lines and cells from bone marrow suggest that CGRP has inhibitory influences on early B cell development. First, CGRP inhibits IL-1-or LPS-induced expression of the BCR on the 70z/3 pre-B cell line [20]. The 70Z/3 pre-B cell line has been used to study cellular events in the transition from a BCRpre-B cell phenotype to a BCR ϩ immature phenotype [25].…”

Section: Introductionmentioning

confidence: 99%

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Calcitonin gene-related peptide inhibits early B cell development in vivo

Schlomer

Storey

Ciornei

et al. 2006

Journal of Leukocyte Biology

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Recent in vitro studies suggest that calcitonin gene-related peptide (CGRP) inhibits early B cell differentiation; however, there is no evidence in the intact animal for a role for CGRP in B cell development. Here, we show that in vivo treatment of mice with CGRP reduces the number of IL-7 responsive B cell progenitors in bone marrow. A single CGRP treatment reduces IL-7-responsive B cell progenitors by up to 40% for up to 72 h. The reduction is dose-dependent and can be blocked by a CGRP receptor antagonist, CGRP(8-37). CGRP in serum following injection is highly elevated at 30 min but returns to basal levels by 4 h, suggesting that a single injection of CGRP has long-lasting effects on B cell development. This report provides the first direct in vivo evidence that CGRP, a neuropeptide with multiple effects on mature lymphocytes, also plays a regulatory role in early B cell development in the bone marrow.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Calcitonin gene-related peptide inhibits early B cell development in vivo

Schlomer

Storey

Ciornei

et al. 2006

Journal of Leukocyte Biology

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“…The effect of CGRP on early B cell differentiation has been examined using a pre-B cell line population (70Z/3). CGRP inhibited the expression of surface immunoglobulin in response to LPS (McGillis et al, 1993, 1995). These studies suggest a crucial role for CGRP in early B cell differentiation, a finding supported by later studies (Fernandez et al, 2000; Schlomer et al, 2007).…”

Section: Cgrp Regulates Lymphocyte Differentiation and Cytokine Produmentioning

confidence: 99%

Calcitonin gene-related peptide is a key neurotransmitter in the neuro-immune axis

2014

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The question of how the neural and immune systems interact in host defense is important, integrating a system that senses the whole body with one that protects. Understanding the mechanisms and routes of control could produce novel and powerful ways of promoting and enhancing normal functions as well as preventing or treating abnormal functions. Fragmentation of biological research into specialities has resulted in some failures in recognizing and understanding interactions across different systems and this is most striking across immunology, hematology, and neuroscience. This reductionist approach does not allow understanding of the in vivo orchestrated response generated through integration of all systems. However, many factors make the understanding of multisystem cross-talk in response to a threat difficult, for instance the nervous and immune systems share communication molecules and receptors for a wide range of physiological signals. But, it is clear that physical, hard-wired connections exist between the two systems, with the key link involving sensory, unmyelinated nerve fibers (c fibers) containing the neuropeptide calcitonin gene-related peptide (CGRP), and modified macrophages, mast cells and other immune and host defense cells in various locations throughout the body. In this review we will therefore focus on the induction of CGRP and its key role in the neuroimmune axis.

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“…Additional experiments demonstrated that inhibition of the antigenpresenting capability of EC by CGRP-I could be completely blocked by CGRP- vasodilating properties (18). CGRP also has modulatory effects on immunocompetent cells such as T cells (10), B cells (19), and MO (20). CGRP also inhibits the antigen-presenting capability of LC (2).…”

Section: Isolation Of Lc From Murine Ec Suspensions and Campmentioning

confidence: 99%

Specific induction of cAMP in Langerhans cells by calcitonin gene-related peptide: relevance to functional effects.

Asahina

Moro

Hosoi

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

121

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Epidermal Langerhans cells (LC) are associated anatomically with epidermal nerves, and a product of these nerves, calcitonin gene-related peptide (CGRP), inhibits the antigen-presenting capacity of LC and macrophages. As the CGRP receptor appears to be coupled to Gs a protein, which in turn activates adenylate cyclase, the ability of CGRP to induce cAMP in LC was examined and correlated with functional effects. LC were isolated from murine epidermal cells using antibodies on magnetic microspheres. Exposure to CGRP induced a significant increase in cAMP content, which could be inhibited by coculture with a truncated form of CGRP ] that is a specific competitive inhibitor of CGRP. Substance P and calcitonin failed to induce cAMP in LC. Although culture in CGRP reduced the ability of murine epidermal cells enriched for LC content to present pigeon cytochrome c to a responsive clone or to present antigen for elicitation of delayed-type hypersensitivity in immune mice, culture in forskolin had little or no effect on antigen presentation despite increased cAMP content of LC as much or more than that induced by CGRP. The effect of CGRP on antigen presentation in these systems could be blocked with CGRP-(8-37). CGRP inhibited the induction of B7-2 by lipopolysaccharide on peritoneal macrophages and a LC line, whereas calcitonin did not. CGRP induces specific accumulation of cAMP in LC and inhibits LC antigen-presenting function by a receptor-mediated event. However, the induction of cAMP by itself does not account for inhibition of antigen presentation. Suppression of the expression of B7-2 may be one mechanism by which CGRP inhibits antigen presentation.Langerhans cells (LC) are dendritic antigen-presenting cells in the skin that play a key role in the cutaneous immune system (1). We have recently discovered an anatomical association between LC and peripheral nerves and have hypothesized that the nervous system regulates the function of LC via release of neuron-derived factors, resulting in the modulation of cutaneous immune responses (2). In particular, calcitonin generelated peptide (CGRP), a major neuropeptide of peripheral sensory nerves (3), was found on the surface of some epidermal LC, and CGRP inhibited the antigen-presenting function of LC in some assay systems (2). We aimed to elucidate this relationship further and to obtain direct evidence for the presence of specific receptors for CGRP on LC.Many neuropeptides (4), as well as many neurotransmitters (5), transduce signals through specific membrane receptors that belong to the large family of G protein-coupled receptors.Two major second-messenger systems, the cAMP-protein kinase A pathway and the phosphatidylinositol-protein kinase C (PKC) pathway, are activated through G proteins, and several ion channels are also modulated by second-messenger systems coupled to G proteins (6). The CGRP receptor appears to be coupled to Gs a subunit, which in turn activates adenylate cyclase (7). Increases in cellular cAMP concentration and/or adenylate cyclase a...

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Modulation of B Lymphocyte Differentiation by Calcitonin Gene-Related Peptide (CGRP)

Cited by 35 publications

References 0 publications

Calcitonin gene-related peptide inhibits early B cell development in vivo

Calcitonin gene-related peptide inhibits early B cell development in vivo

Calcitonin gene-related peptide is a key neurotransmitter in the neuro-immune axis

Specific induction of cAMP in Langerhans cells by calcitonin gene-related peptide: relevance to functional effects.

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