Cell death in allergic diseases.
Apoptosis, the most common form of cell death, is a key mechanism in the build up and maintenance of both innate and adaptive immunity. Central to the apoptotic process is a family of intracellular cysteine proteases with aspartate-specificity, called caspases. Caspases are counter-regulated by multiple anti-apoptotic molecules, and the expression of the latter in leukocytes is largely dependent on survival factors. Therefore, the physiologic rates of apoptosis change under pathologic conditions. For instance, in inflammation, the expression of survival factors is usually elevated, resulting in increased cell survival and consequently in the accumulation of the involved immune cells. In many allergic diseases, eosinophil apoptosis is delayed contributing to both blood and tissue eosinophilia. Besides eosinophils, apoptosis of other leukocytes is also frequently prevented or delayed during allergic inflammatory processes. In contrast to inflammatory cells, accelerated cell death is often observed in epithelial cells, a mechanism, which amplifies or at least maintains allergic inflammation. In conclusion, deregulated cell death is a common phenomenon of allergic diseases that likely plays an important role in their pathogenesis. Whether the apoptosis is too little or too much depends on the cell type. In this review, we discuss the regulation of the lifespan of the participating leukocytes in allergic inflammatory responses.
Simon
Hans-Uwe
HU
Institute of Pharmacology, University of Bern, Bern, Switzerland. hus@pki.unibe.ch
D017209:Apoptosis / Q000276:immunology*; D020169:Caspases / Q000502:physiology; D016923:Cell Death; D002470:Cell Survival; D016207:Cytokines / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism / Q000473:pathology*; D007107:Immune System / Q000502:physiology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D020169:Caspases