Up-regulation of alveolar macrophage platelet-derived growth factor-B (PDGF-B) mRNA by interferon-gamma fromMycobacterium tuberculosisantigen (PPD)-stimulated lymphocytes

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Abstract
SUMMARY: Macrophage production of PDGF-B is believed to be important in the pathogenesis of diseases where chronic lung inflammation develops into fibrosis. Since tuberculosis is characterized by chronic inflammation and tissue fibrosis, we asked if lymphokincs from lymphocytes stimulated by the Mycobacterium tuberculosis antigen PPD, contained factors capable of increasing human alveolar macrophage PDGF-B mRNA. Supernatants from both phytohaemagglutinin (PHA)- and purified protein derivative (PPD)-stimulated lymphocytes, when added lo macrophages. induced an increase in the mRNA of PDGF-B, but not transforming growth factor-beta (TGF-β). When lymphocytes from contacts of patients with tuberculosis, patients with tuberculosis, and normal subjects were compared following PPD stimulation, the lymphocytes from the contacts had the greatest proliferation response, the greatest production of inierferon-gamma (IFN-γ), and their lymphokincs induced the greatest increase in PDGF-B mRNA in macrophages. Recombinant human IFN-γ reproduced this ability of lymphokines to increase macrophage PDGF-B mRNA. Finally, the increase in macrophage PDGF-B mRNA following incubation with supernatants from PPD-stimulated lymphocytes was shown to be due to IFN-γ, when the increase in macrophage PDGF-B mRNA was prevented by addition of anti-human IFN-γ antibody to the lymphocyte supernatant This study indicated that antigen-stimulated lymphocytes released IFN-γ. which in turn resulted in an increase in PDGF-B mRNA in alveolar macrophages. Such a mechanism provides a link between the DTH response and the first stages of a fibrotic reaction, and may offer an explanation for the progression of chronic inflammation lo fibrosis, as occurs in the lungs of patients with untreated pulmonary tuberculosis.

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