Microenvironmental Factors that Influence Mast Cell Phenotype and Function

Abstract

Mast cells play a central role in immediate hypersensitivity responses. They produce and store in their numerous cytoplasmic granules, and synthesize de novo when activated, an array of biologically potent substances whose combined effects account for the many symptoms of allergic reactions. It is, however, difficult to believe that mast cells evolved to serve in such pathological processes. Yet, despite having first been described over a century ago (1), we still know little about the physiologic functions of these cells.

Complicating efforts to understand the biology of mast cells is their heterogeneous nature (see below). In rats, mice, and humans, two phenotypically distinct subsets of mast cells have been identified (2–4), although it is likely that these represent merely two points in a spectrum of diversity (e.g., see Ref. 5). Sorting out the causes of this diversity should lead to a better understanding of the importance of mast cells in health and disease.

Recent evidence suggests that mast cell heterogeneity may largely be due to the site-specific blending of factors produced within the local microenvironment (2). Therefore, it is critical to identify these factors and determine precisely how they affect mast cell phenotype. Accordingly, in this review we will examine the most recent findings which suggest that factors released or expressed by other cells in the vicinity of mast cells may regulate their form and function.

Mast Cell Heterogeneity and Plasticity

Mast cells in the peritoneal cavity of rats and mice are easily obtained by lavage. In contrast, other mast cell populations require enzymatic digestions to disperse them from the tissues in which they are found. Since peritoneal mast cells share many similarities with those in most other parts of the body, they are widely used and have by default come to represent the prototypical mast cell.