The Role of Mast Cells in Inflammatory Processes: Evidence for Nerve/Mast Cell Interactions

Abstract

In the rat, there is considerable evidence of mast cell/nerve interaction both in the normal and infected intestine. Between 67 and 87% of all mast cells in the intestinal lamina propria of rats infected 22–35 days earlier with Nippostrongylus brasiliensis were touching nerves. These membrane contacts were between subepithelial mast cells and nonmyelinated nerves containing substance P, calcitonin gene-related peptide and neurone specific enolase. 2.5S nerve growth factor (NGF) has a significant enhancement effect on antigen-induced histamine release without addition of phosphatidylserine, and the in vivo administration of NGF to rats causes both connective tissue and mucosal mast cells to dramatically increase in number. All of these effects are both dose dependent and NGF specific, as evidenced by inhibition with anti-NGF. 2.5S NGF also causes in vitro increase of colonies in methylcellulose cultures of human peripheral blood. The effects of NGF in this system are synergistic with other T cell-derived growth factors and relatively specific for metachromatic cell growth. These observations support the conclusions that nerves and mast cells may constantly communicate and provide a structural and conceptual framework whereby the central nervous system may communicate with inflammatory events.

Ablation of TrkA function in the immune system causes B cell abnormalities

“…B-and T-cell number and distribution in spleen, thymus, bone marrow and blood appear unaffected by TrkA deletion. Similar results have been obtained for mast cells in skin, spleen and lymph nodes despite reports that NGF injections cause their increase in various tissues of neonatal rats (Aloe and Levi-Montalcini, 1977;Bienenstock et al, 1987;Bullock and Johnson, Jr, 1996). This is a striking result because many studies suggested that disruption of the NGF/TrkA system in the immune system would cause dramatic deficits.…”

Nerve growth factor promotes human hemopoietic colony growth and differentiation.

“…Basophil/mast cell and eosinophil differentiation-promoting factors are produced by human nasal polyp and allergic rhinitis mucosal epithelial scrapings in vitro, suggesting the importance of locally derived factors in the regulation of numbers of these specialized granulocytes in allergic inflammation (17,18). We have also shown extensive mast cell/nerve structural membranemembrane associations in normal and inflamed rat intestines (9,10). Mast cell/nerve interactions may be important in various forms of neurogenic inflammation, in vivo and in the homeostatic regulation of various internal physiologic parameters (19)(20)(21)(22).…”

“…NGF is secreted by fibroblasts (46) and can induce in dose-dependent manner significant increases in mast cell numbers of both mucosal and connective tissue type, according to their normal predominance in a particular tissue, after injection into neonatal rats (8,9). Since NGF can also promote the effect of T-cellderived lymphokines or induce T cells to secrete CSA, NGF may play a significant role in both inflammation and tissue repair, as has already been suggested in wound-healing experiments (2,7).…”

“…For example, NGF causes degranulation of rat peritoneal mast cells (5), induces shape changes in platelets (6), and accelerates wound healing (2, 7). Since NGF injections in vivo cause mast cell numbers to increase in various tissues of neonatal rats (8)(9)(10)(11), we explored the effect of NGF on human hemopoietic colony formation, with particular emphasis on basophil/mast cell colonies.…”

Mast cells synthesize, store, and release nerve growth factor

“…Mast cells are involved in inflammatory and hypersensitivity reactions (1) and occur in many peripheral tissues, in perivascular regions in close apposition to innervating sensory or autonomic nerve fibers (2), and also within the peripheral and central nervous systems (3). Nervous and immunological mediators such as neuropeptides or IgE can affect the state of mast cell activation (4).…”