Mast cells in cutaneous inflammatory disorders.

Mast cells in skin are distributed around dermal and subcutaneous blood vessels. Activation of tissue mast cells produces secretion and/or generation and secretion of a variety of biologically active molecules. Mast-cell-dependent mediators may be classified as smooth-muscle-contracting and vasoactive activities, chemotactic factors, enzymes, and proteoglycans. These mediators alter the microenvironment to produce a biphasic response. The initial or humoral phase of the response is mediated by materials that alter vascular permeability; peripheral blood leukocytes attracted by chemotactic factors establish the cellular phase. Failure to limit the humoral phase creates a pharmacologic state that may be recognized in skin as urticaria/angioedema. The inability to control the cellular phase permits progression to a local inflammatory state with subacute and chronic tissue injury recognized in skin, for example, as necrotizing vasculitis. As an example of the former, certain forms of physical urticaria have provided experimental models in humans to allow observation of the clinical manifestations, study of tissue alterations by histologic analysis, measurement of mediators released into the circulation, and assessment of motility of peripheral blood leukocytes. An example of the role of the mast cell in the production of subacute and chronic inflammatory cutaneous disease is suggested by studies in a patient in whom exposure to the physical stimuli of cold and trauma was followed by initial mast cell degranulation, subsequent tissue deposition of circulating immune complexes, and the development of a necrotizing vasculitis.