title: Phenotypes of infiltrating cells in trehalose dimycolate-induced interstitial pneumonitis.
abstract: Trehalose dimycolate is a glycolipid component of the cell walls of mycobacteria, nocardia, and corynebacteria. When trehalose dimycolate is injected into certain strains of mice, they develop interstitial pneumonitis that is characterized by mononuclear cell infiltration of the alveolar walls, intra-alveolar hemorrhages, and in some animals, granuloma formation. The disorder is seldom fatal, and in approximately 4 weeks, the lungs are normal. There is strong evidence that T lymphocytes are essential for production of interstitial pneumonitis by trehalose dimycolate, but little is known about the mechanisms of lung injury in this model. The experiments described in this report were conducted to identify the roles of the various cells that accumulate in the lungs of mice with this form of interstitial pneumonitis. We found that Mac3+ macrophages were the first cells to appear in the alveolar walls. Increases in the number of L3T4+ T lymphocytes, Lyt2+ T lymphocytes, and surface-immunoglobulin-positive lymphocytes followed, but significant increases in the number of lymphoid cells were not observed until day 7, when the pulmonary lesions were well developed. Treatment of the mice with cyclophosphamide or anti-T-cell sera significantly reduced the number of lymphoid cells in the alveolar walls but did not affect the number of Mac3+ cells and did not affect development of intra-alveolar hemorrhages. Treatment with poly(I.C) significantly decreased the number of Mac3+ cells in the lungs, and these mice did not develop pulmonary hemorrhages. We conclude that although development of pulmonary lesions in trehalose dimycolate-treated mice is a T-cell-dependent process, macrophages are also essential and are more directly involved in production of the lung injury. We postulate that the lung lesions are the direct effect of macrophage-produced cytokines, such as tumor necrosis factor.
authors.affiliation: Conrad D. Stephenson Laboratory, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: M B
authors.initials: MB
authors.lastname: Goren
authors.forename: C H
authors.initials: CH
authors.lastname: Kirkpatrick
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003311:Cord Factors / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005677:G(M1) Ganglioside; D006017:Glycolipids / Q000008:administration & dosage*; D006028:Glycosphingolipids / Q000276:immunology; D007106:Immune Sera / Q000008:administration & dosage; D008214:Lymphocytes / Q000145:classification / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011070:Poly I-C / Q000008:administration & dosage; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology / Q000473:pathology*
chemical_list: D003311:Cord Factors; D006017:Glycolipids; D006028:Glycosphingolipids; D007106:Immune Sera; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D003520:Cyclophosphamide; D011070:Poly I-C