Effect of recombinant interleukin-5, interleukin-3, and eotaxin on apoptosis in eosinophilic granulocytes

Abstract

We studied in vitro effects of recombinant interleukin-5, interleukin-3, and eotaxin on programmed death of eosinophils from healthy donors and patients with non-Hodgkin's lymphomas associated with severe blood eosinophilia. Interleukin-5 and eotaxin produced the most potent antiapoptotic effect on eosinophils from healthy donors. In patients with non-Hodgkin's lymphomas, spontaneous apoptosis in eosinophilic leukocytes was low and remained unchanged during incubation with recombinant proteins.

Molecular Mechanisms of the Effect of Interleukin-2 on Apoptosis of Blood Lymphocytes

“…A possible mechanism underlying the blockade of glucocorticoid-induced apoptosis by recombinant IL-2 is its capacity to initiate the proliferative cascade by JAK/STAT, PI3K, or MAPK signal pathways converging on the regulation of the expression of bcl-2 gene; up-regulation of bcl-2 gene expression results in cell survival and proliferation [6]. This assumption is confi rmed by a well-known capacity of glucocorticoids to inhibit the synthesis of antiapoptotic [2] and stimulate the synthesis of proapoptotic Bcl-2 family proteins [6,15], which leads to activation of the apoptotic program in the cell [11]. Moreover, we previously showed that binding of STAT5 and AP 1 proteins activated by IL-2 to glucocorticoid receptor prevents the formation of complexes of these receptors with cofactors CBP/ p300 or SRC-1a, which blocks the transduction of the proapoptotic signal [3] Mitochondrial factors (cytochrome C, AIF, calcium ions, Apaf-1, etc.)…”

“…This mechanism limits the immune response after death of the pathogen. Apoptosis of T cells can be reduced or abolished by cytokines, whose receptors have common γ-chain (IL-2, IL-4, IL-7, IL-15, and IL-21) [2]. Excessive antigenic stimulation leads to antigen-induced apoptosis of T cells.…”