Cell death in allergic diseases

Abstract

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.

Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils

“…The exact mechanisms how the survival-prolonging cytokines IL-5 and GM-CSF induce eosinophil survival or glucocorticoids induce eosinophil death are not known in detail [3,22,30]. In fact, it is not even known whether glucocorticoid-induced apoptosis involves mainly transcriptional activation or repression [39].…”

“…Inhibition of JNK activity by the cell permeable inhibitory peptide L-JNKI1 almost completely abolished TSA-enhanced DNA breakdown, suggesting a role for JNK. Even though the involvement of caspases in apoptosis in general is well established, surprisingly little is known of the role caspases in human eosinophils [3,30] and the actual caspases mediating apoptosis in human eosinophils remain largely unknown [3,30]. General caspase inhibitors Q-Vd-OPh and Z-Asp-CH2-DCB completely antagonized the effect of TSA on apoptosis in human eosinophils similarly to inhibitors of caspases 6 and 3, whereas inhibition of caspase 8 had no effect.…”

Hypothesis for a common-cause underlying both autoimmune-diseases and allergies

“…These proteins are highly conserved and are homologous to proteins found in humans (Valenta et al, 2009;Garn et al, 2007;Simon, 2009). …”

Different anti-apoptotic effects of house dust mite allergen on eosinophil apoptosis between atopic and non-atopic asthmatic subjects

“…Delayed eosi nophil apoptosis induces persistent inflammation and tissue damage, which evoke or aggravate clinical features of asthma. The antiapoptotic mechanism of eosi nophils is involved in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, JAK/STAT pathway and caspase cascade 12,14 .…”