Bone Marrow-Derived Macrophages Express Functional CGRP Receptors and Respond to CGRP by Increasing Transcription of c-fos and IL-6 mRNA

Endogenous NGF regulates CGRP expression in human monocytes, and affects HLA-DR and CD86 expression and IL-10 production

“…by guest www.bloodjournal.org From Sensory neurons innervate the parenchyma of primary and secondary lymphoid organs 51 and CGRP binding sites have been found in spleen, thymus, bone marrow, and purified immune-cell populations. [24][25][26][27]51,52 Thus, in addition to its direct effects on immune-cell functions, NGF may influence inflammatory responses by regulating the synthesis of CGRP in either sensory nerves or immune cells.…”

“…A wide range of CGRP effects has been described in in vitro and in vivo experiments, [27][28][29][30][31][32][33][34][35][36]53,54 showing that CGRP can influence key processes of the immune response and exert an anti-inflammatory action. The main effect of CGRP administration both in vitro and in vivo is to dampen the immune response essentially by affecting antigen presentation in a variety of APCs such as Langerhans cells, dendritic cells, monocytes, and macrophages.…”

“…[24][25][26][27]51,52 Thus, in addition to its direct effects on immune-cell functions, NGF may influence inflammatory responses by regulating the synthesis of CGRP in either sensory nerves or immune cells.…”

“…Specific receptors for CGRP are present in T and B lymphocytes and in macrophages, [24][25][26][27] and several in vitro studies have demonstrated that CGRP is a potent inhibitor of mitogen and antigen-stimulated proliferation of T-cells, 28-31 and of antigen presentation by macrophages. 32,33 In vivo data indicate an anti-inflammatory action of CGRP, since its administration inhibits edema formation induced by inflammatory mediators, prevents the induction of contact hypersensitivity, and influences the migration of monocytes and antigen presentation.…”

“…[10][11][12][13][14][15] The immune cells that produce NGF also express the specific NGF receptor tyrosine receptor kinase A (TrkA) 16 which, on binding to its ligand, activates intracellular pathways and nuclear factors [17][18][19][20] in a manner similar to what happens in neuronal cells. 21 In vitro, the administration of NGF to purified myeloid-or lymphoid-cell populations influences a wide range of functions: the release of inflammatory mediators, chemotaxis, the production of cytokines and immunoglobulins, proliferation, and survival (for a review see Aloe et al 22 ).In spite of the large number of studies on the in vitro effects of NGF, it is still not clear why NGF is produced in vivo during the inflammation process and how its local synthesis, often in an autocrine fashion, can influence the ongoing immune response.Our recent results on autocrine NGF synthesis in B lymphocytes, which directly regulate the expression and release in these cells 23 of calcitonin gene-related peptide (CGRP), a neuropeptide able to inhibit immune response, indicate that NGF may have an anti-inflammatory action.Specific receptors for CGRP are present in T and B lymphocytes and in macrophages, [24][25][26][27] and several in vitro studies have demonstrated that CGRP is a potent inhibitor of mitogen and antigen-stimulated proliferation of T-cells, 28-31 and of antigen presentation by macrophages. 32,33 In vivo data indicate an anti-inflammatory action of CGRP, since its administration inhibits edema formation induced by inflammatory mediators, prevents the induction of contact hypersensitivity, and influences the migration of monocytes and antigen presentation.…”