PI3K, ERK, p38 MAPK and integrins regulate CCR3-mediated secretion of mouse and human eosinophil-associated RNases.

摘要: Background Eosinophils have the capacity to secrete varied cytotoxic proteins. Among proteins are eosinophil-associated RNases (EARs): human eosinophil-derived neurotoxin and eosinophilic cationic protein, their murine ortholog EARs, which been shown be involved in host defense, tissue remodeling, immunity regulation. However, signal transduction that regulates EARs secretion response physiological stimuli, such as chemokines, has little studied scarcely mouse eosinophils, foremost animal model for diseases. Objective In this study, we aimed understand of enzymatically active following chemokine stimulation. Methods Fresh eosinophils were stimulated with CCL11 CCL24, was detected using an RNase activity assay. The involvement signaling factors or integrins probed specific inhibitors blocking antibodies. Adhesion evaluated by microscopy. Results We found to CCL11 CCL24 Gαi-dependent. Both required activation PI3K, ERK, p38 MAPK. In addition, adhesion molecules β1 β2 crucial EAR secretion, suggest a mechanism spreading is obligatory secretion. Conclusions Collectively, these data common CCR3-mediated pathway leads both eosinophils. These findings applicable eosinophil-mediated defense diseases.