Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor.
Resident pulmonary alveolar macrophages (PAM) play an important role in the maintenance of immunological homeostasis in the lung via downmodulation of local T cell responses in the steady state. The present study demonstrates that this pathway for T cell suppression is reversible via granulocyte/macrophage colony-stimulating factor (GM-CSF). Thus, freshly isolated PAM strongly inhibit mitogen-induced T cell proliferation, and pretreatment of the PAM with cytokine-rich lung-conditioned medium (LCM) generated by exposure of lung to bacterial lipopolysaccharide (LPS) abrogated this suppressive activity. LCM from lungs of normal and athymic nude mice exhibited identical activity. Moreover, the PAM-modulating activity of LCM was inhibited by blocking antibody specific for GM-CSF, and the activity of LCM could be reproduced by recombinant GM-CSF. This suggests that secretion of GM-CSF by mesenchymal cells and/or macrophages under stimulation from agents such as LPS provides a potential mechanism for upregulation of local T cell responsiveness during acute inflammation. In addition, experiments with a range of cytokines indicated that interleukin 4, transforming growth factor beta 1 and tumor necrosis factor alpha (TNF-alpha) exhibited weaker (but significant) modulatory effects on PAM, and (in the case of TNF-alpha) amplified the effects of GM-CSF.
Bilyk
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Division of Cell Biology, Western Australian Research Institute for Child Health, Subiaco.
Holt
P G
PG
D000818:Animals; D017077:Culture Media, Conditioned; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects*; D008168:Lung / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017077:Culture Media, Conditioned; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor