Expression of ICAM-1 and TNF alpha in human alveolar macrophages from lung-transplant recipients.
Local activation of macrophages may play an important role in the immune process of pulmonary infections and in the inflammatory response of lung allograft rejection. To document macrophage activation within human lung allografts displaying various complications, we have investigated ICAM-1 expression in freshly isolated alveolar macrophages (AM) from lung-transplant recipients by immunocytofluorimetric analysis, and rIFN gamma induced in vitro by ELISA. A total of 21 bronchoalveolar lavage fluids (BAL) from 13 transplanted patients displaying no complication, acute rejection, bacterial/fungal infection, or CMV infection entered the study. ICAM-1 was expressed at a higher level in rejecting patients. Surprisingly, TNF alpha release from AM upon in vitro activation was significantly decreased during rejection. Furthermore, we have studied the effects of the glucocorticoid dexamethasone, the key drug for the treatment of allograft rejection, on the expression of ICAM-1 and TNF alpha induced in vitro in AM, at the levels of protein production and of transcription. Whereas dexamethasone did not influence ICAM-1 expression in AM, it downregulated TNF alpha production at least in part at the transcriptional level. Our results suggest strongly that the anti-inflammatory effects of corticosteroids are not related to ICAM-1 modulation on human AM but to the downregulation of the proinflammatory cytokine TNF alpha that is produced early in the inflammatory process. Moreover, our model of human AM activation induced in vitro by rIFN gamma appears a useful tool for in vitro investigation of the cellular and molecular targets of anti-inflammatory drugs for a more appropriate use.
Laboratory of Immunology, CNRS URA 1159, University of Paris-XI, Le Plessis-Robinson, France.
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M
Fattal-German
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Le Roy Ladurie
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F
Lecerf
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Berrih-Aknin
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D016040:Lung Transplantation; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone; D007371:Interferon-gamma