ABSTRACT
Inhalation of Saccharopolyspora rectivirgula causes "farmer's lung" disease, a classic example of hypersensitivity pneumonitis (HP). Monocyte chemoattractant protein-1 (MCP-1) is increased in the bronchoalveolar lavage fluid of mice challenged with S rectivirgula, and S rectivirgula induces MCP-1 secretion by alveolar macrophages. We tested the hypothesis that MCP-1 and its receptor CC chemokine receptor-2 (CCR2) are essential to the development of experimental HP by treating mice with MCP-1 antibody and using CCR2(-/-) mice. Administration of anti-MCP-1 did not change the response to intratracheally administered S rectivirgula. CCR2(-/-) animals responded in a fashion similar to that of wild-type animals to intratracheally administered.S rectivirgula. To determine the influence of the MCP-1-CCR2 interaction in vitro, we transferred S rectivirgula-cultured spleen cells from S rectivirgula-sensitized mice, to naïve recipients. Later, challenge of the recipients with intratracheal S rectivirgula and examination of both lung histology and bronchoalveolar lavage fluid characteristics were used to determine whether adoptive transfer had occurred. We found that cultured cells from CCR2(-/-) animals were fully capable of adoptive transfer. We conclude that interaction of MCP-1 with CCR2 is not necessary for the development of pulmonary inflammation in response to intratracheally administered S rectivirgula or cells able to adoptively transfer experimental HP.
Subject(s)
Alveolitis, Extrinsic Allergic/immunology , Alveolitis, Extrinsic Allergic/metabolism , Chemokine CCL2/metabolism , Receptors, Chemokine/genetics , Adoptive Transfer , Alveolitis, Extrinsic Allergic/microbiology , Animals , Antibodies/pharmacology , Chemokine CCL2/immunology , Farmer's Lung/immunology , Farmer's Lung/metabolism , Farmer's Lung/microbiology , Male , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Receptors, CCR2 , Receptors, Chemokine/metabolism , Saccharopolyspora , Spleen/cytologyABSTRACT
Inhalation of Saccharopolyspora rectivirgula (SR) can cause the disease Farmer's Lung, a classic example of hypersensitivity pneumonitis. Th1, but not Th2, cell lines can adoptively transfer experimental hypersensitivity pneumonitis (EHP). Substantial amounts of IL12 appear in bronchoalveolar lavage fluid (BALF) after a single intratracheal (IT) injection of SR, and SR-induced IL12 secretion by both a macrophage cell line and alveolar macrophages. We tested the hypothesis that IL12 is essential for the development of EHP by addition of anti-IL12 to cultured cells, and adoptive transfer of EHP in IL12p40-/- animals. We transferred SR cultured spleen and lung associated lymph node cells from SR sensitized mice (both IL12p40-/- and wild type), to naïve recipients (both wild type and IL12p40-/-). The addition of anti-IL12 to cultures of sensitized cells could not ablate the ability of these cells to transfer EHP. Cultured cells from IL12p40-/- animals were fully capable of transferring EHP. In contrast, IL12p40-/- recipients of both wild type and IL12p40-/--cultured cells were less able to express EHP (lung histology and BALF characteristics) than wild type mice, and had more eosinophils in both lung tissue and BALF. We conclude that IL12 is not necessary for development of cells able to adoptively transfer EHP, but that it is required for full expression of EHP in recipient animals.
