The phylogenetic profile of mast cells

Mast cells (MCs) are tissue-based immune cells that participate to both innate and adaptive immunities as well as to tissue-remodelling processes. Their evolutionary history appears as a fascinating process, whose outline we can only partly reconstruct according to current remnant evidence. MCs have been identified in all vertebrate classes, and a cell population with the overall characteristics of higher vertebrate MCs is identifiable even in the most evolutionarily advanced fish species. In invertebrates, cells related to vertebrate MCs have been recognized in ascidians, a class of urochordates which appeared approximately 500 million years ago. These comprise the granular hemocyte with intermediate characteristics of basophils and MCs and the “test cell” (see below). Both types of cells contain histamine and heparin, and provide defensive functions. The test cell releases tryptase after stimulation with compound 48/80. A leukocyte ancestor operating in the context of a primitive local innate immunity probably represents the MC phylogenetic progenitor. This cell was likely involved in phagocytic and killing activity against pathogens and operated as a general inducer of inflammation. This early type of defensive cell possibly expressed concomitant tissue- reparative functions. With the advent of recombinase activating gene (RAG)-mediated adaptive immunity in the Cambrian era, some 550 million years ago, and the emergence of early vertebrates, MC progenitors differentiated towards a more complex cellular entity. Early MCs probably appeared in the last common ancestor we shared with hagfish, lamprey, and sharks about 450-500 million years ago.