Mast cell functions

The in vivo relevance and biological importance of in vitro observations about mast cell function, as well as the contributions of mast cells towards the expression of particular biological responses (such as various models of anaphylaxis) in vivo, can be assessed using c-kit mutant mice (e.g., WBB6Fi-FCit or mice) that virtually lack mast cell populations. Mice with mutations of c-kit [6,11] or mutations that affect KIT expression [12-14] have other abnormalities of phenotype besides a mast cell deficiency. However, the mast cell deficiency of these mice can be selectively repaired by the adoptive transfer of genetically compatible, in vitro-derived... 

Factors Modulating (or Tuning ) FceRI-Dependent Mast Cell Functional Activation... 

Liu Y Zhu M, Nishida K, Hirano X Zhang W An essential role for RasGRP 1 in mast cell function and IgE-mediated allergic response. J Exp Med 2007 204 93-103. 

M, Altruda F, Hirsch E, Wymann MP Phos- 75 phoinositide 3-kinase y is an essential amplifier of mast cell function. Immunity 2002 16 441-451. 

PEPTIDES THAT AFFECT MAST CELL FUNCTION 149... 

In order to influence mast-cell function, peptides must be made available at sites very near to tissue mast cells. One means of accomplishing this is by specific peptidergic innervation. This would not necessarily require a classical synaptic morphology, but only the termination of nerves within the vicinity of mast cells [1,3]. Modulation of mast-cell secretion by peptides of neural origin is particularly attractive, for it would allow for a restricted, localized expression of peptide action in specific target tissues because of the selective distribution of each peptide within particular neurones. Moreover, this could be further modified and restricted by differing mast cell specificities. (Heterogeneity of mast cell responsiveness to peptide stimulation has been well documented [52, 53 ].) The result would permit a well-localized tissue response without systemic manifestation [3]. 

Peptidergic nerves are known to innervate tissues with a high mast-cell content and to contain specific peptides which have been demonstrated to affect mast-cell function [5, 54-56]. 

While the majority of attention has focused on peptides contained within the nervous system, two other important methods for delivering peptides to the vicinity of the mast cell have been established (1) peptides produced and secreted by other cells of inflammation that may affect mast-cell function and (2) the local generation of mast-cell-active peptides by secreted enzymes acting on circulating protein precursors. Examples of the former include several, as yet ill-defined, peptide factors and cationic proteins from other immunocompetent cells [66-69], defined lymphokines such as the interleukin-1 [70] and interleukin-3 [71], and tumour necrosis factor [70], Examples of the latter include bradykinin [72] and a recently identified peptide produced by the action of acid proteinases on albumin [73, 74]. 

Table 4.1. IDENTIFIED PEPTIDES AFFECTING MAST-CELL FUNCTION See text for appropriate references unless otherwise indicated, RPMC, rat peritoneal mast cell RMMC, rat mucosal mast cell MBMC, murine bone-marrow derived.

Nigo YI, Yamashita M, Hirahara K, et al Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function. Proc Natl Acad Sci USA 2006 103 2286-2291. 

Mellor, E. A., Frank, N., Soler, D., et al.. (2003) Expression of the type 2 receptor for cysteinyl leukotrienes (CysLT2R) by human mast cells functional distinction from CysLTlR. Proc. Natl. Acad. Sci. U. S. Am. 100,11589-11593. 

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