Stephen J. Galli

Identification of A3 Receptor- and Mast Cell-Dependent and -Independent Components of Adenosine-Mediated Airway Responsiveness in Mice

Adenosine-induced bronchoconstriction is a well-recognized feature of atopic asthma. Adenosine acts through four different G protein-coupled receptors to produce a myriad of physiological effects. To examine the contribution of the A3 adenosine receptor to adenosine-induced bronchoconstriction and to assess the contribution of mast cells to this process, we quantified airway responsiveness to aerosolized adenosine in wild-type, A3 receptor-deficient, and mast cell-deficient mice. Compared with the robust airway responses elicited by adenosine in wild-type mice, both A3-deficient and mast cell-deficient mice exhibited a significantly attenuated response compared with their respective wild-type controls. Histological examination of the airways 4 h after adenosine exposure revealed extensive degranulation of airway mast cells as well as infiltration of neutrophils in wild-type mice, whereas these findings were much diminished in A3-deficient mice and were not different from those in PBS-treated controls. These data indicate that the airway responses to aerosolized adenosine in mice occur largely through A3 receptor activation and that mast cells contribute significantly to these responses, but that activation of additional adenosine receptors on a cell type(s) other than mast cells also contributes to adenosine-induced airway responsiveness in mice. Finally, our findings indicate that adenosine exposure can result in A3-dependent airway inflammation, as reflected in neutrophil recruitment, as well as alterations in airway function.

The Regulation of Mast Cell and Basophil Development by the Kit Ligand, SCF, and IL-3

As noted in the introduction to Chapter 1, the regulation of mast cell and basophil development, and the related area of “mast cell heterogeneity,” are large topics to which many groups have made important contributions. In this chapter, we review current understanding of the effects of two cytokines, the kit ligand, stem cell factor (SCF), and interleukin-3 (IL-3), on mast cell and basophil development. Several other chapters in this book also address aspects of this subject (see Chapters 3, 4, 5, 6, and 7), and many of the topics that are considered in detail in these other reviews are omitted, or discussed only briefly, herein.