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 tissue recruitment of eosinophils in humans as well as in animals. To clarify which types of cells are actually important as sources of human eotaxin, we used a specific enzyme-linked immunosorbent assay (ELISA) to compare various 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 endothelial 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 (on the order of ng/ml). The eotaxin generation was induced by tumour necrosis factor alpha (TNF-alpha) or IL-4, and the production was drastically increased by combined use of these cytokines. Because fibroblasts are ideally situated within the interstium at the sites of allergic responses, our finding that these cells represent an important cellular source of eotaxin suggests that fibroblast-derived eotaxin may act to regulate eosinophil recruitment in a paracrine fashion.
Miyamasu
M
M
Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Tokyo, Japan.
Nakajima
T
T
Misaki
Y
Y
Izumi
S
S
Tsuno
N
N
Kasahara
T
T
Yamamoto
K
K
Morita
Y
Y
Hirai
K
K
D001980:Bronchi; D002460:Cell Line; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D020405:Dermis / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4