Murine hypersensitivity pneumonitis: production and importance of colony-stimulating factors in the course of a lung inflammatory reaction.
The release of colony-stimulating factors (CSFs) and their contribution to the inflammatory response in the lungs of mice exposed by the intranasal route to the actinomycete Faeni rectivirgula (150 micrograms/day, 3 days/wk), an important thermophilic actinomycete that determines farmer's lung in humans, was examined. Bronchoalveolar lavages (BAL) and lung homogenates of normal mice or saline-instilled mice contained undetectable levels (less than 0.5 U/ml) of the cytokines interleukin-3 (IL-3), colony-stimulating factor-1 (CSF-1), and granulocyte/macrophage colony-stimulating factor (GM-CSF). Mice instilled with F. rectivirgula developed a CSF cytokine response early (24 h) after the instillation that increased and plateaued 2 wk later, and stayed high thereafter. Similarly, lung homogenates of F. rectivirgula-challenged mice contained significant levels of all three CSFs from 24 h after treatment until termination of the experiment. The offending agent itself, F. rectivirgula, was found to directly induce the secretion of IL-3 and GM-CSF from isolated mouse BAL cells and mouse splenocytes, at doses ranging from 1 to 100 micrograms/ml. This was not due to contaminating endotoxin, as inclusion of polymyxin B did not modify this release. Instillation of antibodies against the CSFs in mice challenged with F. rectivirgula did not modify the increase in BAL cell number determined by the challenge (11-fold increase in BAL cell number in F. rectivirgula-instilled mice at 3 wk, whether given anti-CSFs or not). Moreover, direct intratracheal infusion of CSFs (5,000 U of IL-3/CSF-1/GM-CSF) every week did not change the cellular response seen in challenged mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Denis
M
M
Pulmonary Research Unit, Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada.
Ghadirian
E
E
D000542:Alveolitis, Extrinsic Allergic / Q000503:physiopathology*; D000818:Animals; D000906:Antibodies; D001992:Bronchoalveolar Lavage Fluid; D003115:Colony-Stimulating Factors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000276:immunology / Q000502:physiology; D007249:Inflammation; D008168:Lung / Q000503:physiopathology*; D016676:Macrophages, Alveolar / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008848:Micromonosporaceae; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000906:Antibodies; D003115:Colony-Stimulating Factors; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha