Our perception of the mast cell from Paul Ehrlich to now

Abstract

Just over a century ago Paul Ehrlich received the Nobel Prize for his studies of immunity. This review describes one of his legacies, the histochemical description of the mast cell, and the research that has ensued since then. After a long period of largely descriptive studies, which revealed little about the biological role of the mast cell, the field was galvanized in the 1950s by the recognition that the mast cell was the main repository of histamine and a key participant in anaphylactic reactions. Although the mast cell was long-viewed in these terms, recent research has now shown that the mast cell also plays a key role in innate and adaptive immune responses, autoimmune disease, and possibly tissue homeostasis by virtue of its expression of a diverse array of receptors and biologically active products. In addition, the responsiveness of mast cells to immunological and pathological stimulants is highly modulated by the tissue cytokine environment and by synergistic, or inhibitory, interactions among the various mast cell receptor systems. This once enigmatic cell of Paul Ehrlich has proved to be both adaptable and multifunctional.

Figure 1

Paul Ehrlich and his sketch of the distribution of mast cells in various tissues in Fig. 1 in [4]. This publication is available on the Paul-Ehrlich-Institut website for Paul Ehrlich.

Figure 2

The postage stamp issued by the Principality of Monaco commemorating the discovery of anaphylaxis. The stamp illustrates the circumstances that resulted in the research of Richet and Portier on anaphylaxis for which Richet received the Nobel prize. Details are described in the text (photograph of a stamp in the author's possession).

Figure 3

Examples of synergistic interactions among mast cell receptors. The figure depicts well-documented examples of receptor ligands that augment responses to antigen either through FcεRI or, in the case of C3a, through FcγRI. Some of these ligands enhance primarily degranulation while others enhance primarily cytokine production. Yellow boxes denote receptor subtypes involved, solid lines denote the responses to antigen via FcεRI or FcγRI, and dashed lines indicate the “feed in” to these responses. The effects on eicosanoid production have not been systematically examined. See text for details and abbreviations.

Figure 4

Mast cell-mediated pathways that lead to innate and adaptive immune responses to pathogenic stimulants. The stimuli could be IgE- or IgG-directed antigens, complement components, TLR ligands, alone or in combination. The innate immune responses include inflammatory responses to histamine and eicosanoids and antimicrobial effects through release of proteases and antibiotic peptides from granules as well as recruitment of leukocytes and macrophages by eicosanoids and chemokines. Adaptive immune responses include cytokine/chemokine-mediated recruitment of naïve T cells and APC to regional lymph nodes for antigen presentation or direct activation of T cells by TNF-α and a costimulatory ligand called OX40L.