This chapter discusses the mechanisms, general and specific, whereby eosinophils and T lymphocytes are recruited into bronchial tissue in asthma.
II. Mechanisms of Cell Accumulation The accumulation of any specific cell type in the lung may reflect enhanced local differentiation of inflammatory cell progenitors and their proliferation, delayed programmed cell death (apoptosis), cell-selective activation together with increased random motility, or activation of cell-specific recruitment mechanisms. For example, levels of eosinophil, mast cell, and basophil progenitors in the blood are increased in asthma, and it is suggested that they receive differentiation and proliferation signals from the inflamed respiratory tissues (2,3). Apoptotic events, an important prelude to the resolution of inflammation, are delayed in eosinophils by the cytokine milieu of the asthmatic airways (4). Thus eosinophils in tissues are likely to live for up to 2 weeks, considerably longer than blood eosinophils,
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which have a half-life of 13-18 hr (5). The increase in the incidence of apoptosis that follows corticosteroid therapy is likely to be due to suppression of the production of granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 5 (IL-5), cytokines that support eosinophil survival. Apoptoptic cells are rapidly cleared by phagocytic tissue macrophages and are therefore detected in small numbers within respiratory tissues. The theory that selective types of blood cells are stimulated to increased random motility proposes that increased selective emigration of the activated cell type occurs across an endothelium that is adhesive for all leukocytes (6). Finally, cell-specific recruitment may be determined by the selective expression of a number of adhesion molecules or chemoattractants (7). Vasodilatation and loss of endothelial integrity are characteristic of the environment in which inflammatory cell recruitment occurs, and modification of endothelial or matrix integrity may further enhance cell recruitment.