Approaches for analyzing the roles of mast cells and their proteases in vivo.
The roles of mast cells in health and disease remain incompletely understood. While the evidence that mast cells are critical effector cells in IgE-dependent anaphylaxis and other acute IgE-mediated allergic reactions seems unassailable, studies employing various mice deficient in mast cells or mast cell-associated proteases have yielded divergent conclusions about the roles of mast cells or their proteases in certain other immunological responses. Such "controversial" results call into question the relative utility of various older versus newer approaches to ascertain the roles of mast cells and mast cell proteases in vivo. This review discusses how both older and more recent mouse models have been used to investigate the functions of mast cells and their proteases in health and disease. We particularly focus on settings in which divergent conclusions about the importance of mast cells and their proteases have been supported by studies that employed different models of mast cell or mast cell protease deficiency. We think that two major conclusions can be drawn from such findings: (1) no matter which models of mast cell or mast cell protease deficiency one employs, the conclusions drawn from the experiments always should take into account the potential limitations of the models (particularly abnormalities affecting cell types other than mast cells) and (2) even when analyzing a biological response using a single model of mast cell or mast cell protease deficiency, details of experimental design are critical in efforts to define those conditions under which important contributions of mast cells or their proteases can be identified.
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA; Microbiology & Immunology, Stanford University School of Medicine, Stanford, California, USA. Electronic address: sgalli@stanford.edu.
Stephen J
SJ
Galli
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Mindy
M
Tsai
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA; GIGA-Research and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium.
Thomas
T
Marichal
Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Elena
E
Tchougounova
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Laurent L
LL
Reber
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Gunnar
G
Pejler
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D010447:Peptide Hydrolases / Q000145:classification / Q000502:physiology*
D007073:Immunoglobulin E; D010447:Peptide Hydrolases
Basophils; Cre recombinase; Mouse model; Stem cell factor; c-kit