Leptin is an eosinophil survival factor

Background

Leptin regulates food intake, as well as metabolic, endocrine, and immune functions. It exerts proliferative and antiapoptotic activities in a variety of cell types, including T cells. Leptin also stimulates macrophages and neutrophils, and its production is increased during inflammation.

Objective

We sought to examine the expression of leptin receptors on eosinophils and the effect of recombinant leptin on proapoptotic pathways in these cells.

Methods

The presence of leptin receptor was examined by means of RT-PCR and immunofluorescence analysis in freshly isolated blood eosinophils and tissue eosinophils. The effect of recombinant leptin on apoptotic pathways in eosinophils was studied by using flow cytometric, immunoblotting, and immunofluorescence techniques.

Results

Human eosinophils express leptin surface receptors under in vitro and in vivo conditions, and leptin delays apoptosis of mature eosinophils in vitro. The antiapoptotic effects of leptin were concentration dependent and blocked by an anti-leptin receptor mAb. The efficacy of leptin to block eosinophil apoptosis was similar to that of GM-CSF. Leptin delayed the cleavage of Bax, as well as the mitochondrial release of cytochrome c and second mitochondria-derived activator of caspase, suggesting that it blocks proapoptotic pathways proximal to mitochondria in eosinophils. Using pharmacological inhibitors, we obtained evidence that leptin initiates a signaling cascade involving phosphatidylinositol-3-OH kinase and mitogen-activated protein kinase–dependent pathways in eosinophils.

Conclusion

Leptin is a survival cytokine for human eosinophils, a finding with potential pathologic relevance in allergic and parasitic diseases.

Key words: Apoptosis, eosinophils, inflammation, leptin, signal transduction

Abbreviations used: ECP, Eosinophil cationic protein, GAPDH, Glyceraldehyde-3-phosphate dehydrogenase, MAPK, Mitogen-activated protein kinase, PI3K, Phosphatidylinositol-3-OH kinase, PS, Phosphatidylserine, Smac, Second mitochondria-derived activator of caspase