Mediators of hypersensitivity pneumonitis.
Inhalation of Saccharopolyspora rectivirgula (S. rectivirgula) causes farmer's lung disease, a classic example of hypersensitivity pneumonitis (HP). HP is characterized by bronchoalveolar lavage fluid (BALF) neutrophilia (within the first 48 hours after inhalation), followed by BALF lymphocytosis. We utilized a well-described murine model of HP to determine the timing of the appearance of the C-C chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha); the inflammatory cytokines tumor necrosis factor (TNF), interleukin-1alpha (IL-1alpha), and interleukin-6 (IL-6); and the Th1 -differentiating cytokine interleukin-12 (IL-12) in BALF. After a single intratracheal administration of S. rectivirgula, there was remarkable BALF neutrophilia (peak 24 to 48 hours), followed by a BALF lymphocytosis (peak 48 to 72 hours) in both C57Bl/6 and BALB/c mice that was preceded by the appearance of MIP-1alpha in BALF (peak 4 to 6 hours) and MCP-1 (peak at 48 hours). In both strains of mice there was a striking increase of BALF IL-12 (peak 48 to 72 hours). There was also an increase in BALF IL-6, IL-1alpha, and TNF that was greater in the BALB/c mice than in the C57Bl/6 mice. S. rectivirgula induced the secretion of MIP-1alpha, MCP-1, IL-6, IL-1alpha, and IL-12 from the murine macrophage cell line J774A.1; MIP-1alpha, IL-6, IL-1alpha, IL-12, and TNF from C57Bl/6 alveolar macrophages; and IL-1alpha, IL-6, and TNF-but not IL-12-from BALB/c alveolar macrophages. We conclude that chemokines and cytokines induced by intratracheal administration of S. rectivirgula precede BALF neutrophilia and lymphocytosis and may cause differentiation of Th1 cells; we also conclude that pulmonary macrophages represent a potential source of these substances.
Schuyler
M
M
Department of Medicine, Albuquerque Veterans Affairs Medical Center, University of New Mexico School of Medicine, 87108, USA.
Gott
K
K
Cherne
A
A
D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count; D008214:Lymphocytes; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008264:Macrophages; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12