Dermal fibroblasts represent a potent major source of human eotaxin: In vitro production and cytokine-mediated regulation

Accumulating evidence indicates that eotaxin plays an integral role in tiss ue recruitment of eosinophils in humans as well as in animals, To clarify w hich types of cells are actually important as sources of human eotaxin, we used a specific enzyme-linked immunosorbent assay (ELISA) to compare variou s types of hemopoietic and nonhemopoietic cells for the ability to produce eotaxin protein. Regardless of various conditioning, we failed to determine any significant eotaxin generation by peripheral leukocytes and vein endot helial cells (less than 20 pg/ml), A small amount of immunoreactive eotaxin was detected in cultures of A549 bronchial epithelial cell line cells. In contrast, dermal fibroblasts were capable of generating extremely high, and potentially biologically relevant, amounts of eotaxin protein (an the orde r of ng/ml), The eotaxin generation was induced by tumour necrosis factor a lpha (TNF-alpha) or IL-4, and the production was drastically increased by c ombined use of these cytokines, Because fibroblasts are ideally situated wi thin the interstium at the sites of allergic responses, our finding that th ese cells represent an important cellular source of eotaxin suggests that f ibroblast-derived eotaxin may act to regulate eosinophil recruitment in a p aracrine fashion. (C) 1999 Academic Press.