Expression and regulation of monocyte chemoattractant protein‐1 by human eosinophils

Abstract

Abstract Several recent studies have identified eosinophils as a cellular source of various cytokines, indicating that eosinophils play not only an effector role, but also a regulatory role within the allergic inflammatory cell network. In this study, we demonstrate that eosinophils can generate and secrete monocyte chemoattractant protein‐1 (MCP‐1), a prototype of C‐C chemokines. Eosinophils generated immunoreactive MCP‐1 in response to such diverse stimuli as C5a, formylmethionyl‐leucyl‐phenylalanine (FMLP) and ionomycin, but MCP‐1 production was not induced by interleukin (IL)‐1 or tumor necrosis factor‐α. C5a‐ and FMLP‐induced eosinophil MCP‐1 production was absolutely dependent on pretreatment with cytochalasin B. Eosinophils elaborated significantly more MCP‐1 than neutrophils. Immunoreactive MCP‐1 was detected at 6 h of incubation with C5a or FMLP. Expression of MCP‐1 mRNA reached a maximum within the first 3 h after stimulation and then declined rapidly to a very low and stable level by 18 h. Pretreatment with IL‐5 markedly amplified C5a‐induced MCP‐1 production, and the enhancement occurred at the pretranslational level. Eosinophilactive chemokines such as eotaxin failed to induce MCP‐1 generation, even when eosinophils were primed by IL‐5. Since MCP‐1 exerts a potent histamine‐releasing effect on human basophils, our results indicate that eosinophils may regulate basophil mediator release with possible consequent contribution to the pathogenesis of allergic inflammation via a paracrine mechanism.