Fibroblast stimulation in schistosomiasis. XII. Identification of CD4+ lymphocytes within schistosomal egg granulomas as a source of an apparently novel fibroblast growth factor (FsF-1).
Granulomas that form around Schistosoma mansoni eggs deposited in the liver secrete a variety of fibrogenic factors that may provide a molecular link between chronic inflammation and hepatic fibrogenesis in schistosomiasis. We recently isolated from conditioned medium of egg granuloma cultures a approximately equal to 60-kDa heparin-binding growth factor for fibroblasts. Because this protein is distinct from other defined heparin-binding growth factors, we designated it "fibroblast stimulating factor-1" (FsF-1). We now report that FsF-1 is a lymphokine. We prepared IgG antibody against purified FsF-1 and determined that it did not cross-react with a variety of growth factors or recombinant interleukins. Using two-color flow cytometry of dissociated granuloma cell suspensions, we observed that approximately 20% to 25% of granuloma CD4+ lymphocytes express surface FsF-1. We isolated CD4+ granuloma lymphocytes by FACS and observed that these cells spontaneously secrete into culture supernatant a fibroblast mitogen that is neutralized by anti-FsF-1 antibody. Furthermore, anti-FsF-1 can specifically immunoprecipitate a metabolically labeled protein produced by the granuloma CD4+ lymphocytes. The labeled protein has the same apparent molecular mass (approximately equal to 60 kDa) as FsF-1 purified from granuloma culture supernatants. These findings define CD4+ lymphocytes as a source of FsF-1. Because FsF-1 has biologic and chemical features distinct from most other defined lymphokines and from other heparin-binding growth factors, FsF-1 appears to be a novel lymphokine.
Division of Geographic Medicine and Infectious Diseases, New England Medical Center Hospitals, Boston, MA 02111.
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Prakash
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Wyler
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000276:immunology / Q000378:metabolism*; D005347:Fibroblasts / Q000473:pathology*; D005434:Flow Cytometry; D006099:Granuloma / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012555:Schistosomiasis mansoni / Q000473:pathology / Q000503:physiopathology*
D005346:Fibroblast Growth Factors