EOKINES - SYNTHESIS, STORAGE AND RELEASE FROM HUMAN EOSINOPHILS

Eosinophils are prominent inflammatory cells in asthma and other aller gic disorders, as well as in helminthic parasite infections. Recently, eosinophils have been reported to synthesize and store a range of reg ulatory proteins within their secretory granules (eokines). Eokines co mprise a group of cytokines, chemokines, and growth factors which are elaborated by eosinophils. These proteins, and the messages which enco de them, appear to be identical to those produced by lymphocytes and o ther tissues. Interestingly, immunoreactivity to many of these eokines has been found to co-localize to the eosinophil's secretory granules. In this review we have discussed the repertoire of 18 eokines so far identified in eosinophils, and focused on four of these, namely, inter leukin-2 (IL-2), IL-4, granulocyte/macrophage colony-stimulating facto r (GM-CSF), and RANTES. These four eokines co-localize to the crystall oid granules in eosinophils, as shown in studies using subcellular fra ctionation and immunogold labeling in electron microscopy. During stim ulation by physiological triggers, for example, with serum-coated part icles, eosinophils release these mediators into the surrounding supern atant. In addition, eokines are likely to be synthesized within eosino phils rather than taken up by endocytosis, as show in detection of mRN A for each of these proteins using in situ hybridization, RT-PCR, and in the case of RANTES, in situ RT-PCR. Eokines synthesis and release f rom eosinophils challenges the commonly held notion that these cells a ct downstream of key elements in immune system, and indicate that they may instead belong to the afferent arm of immunity.