Articles in PresS. Am J Physiol Lung Cell Mol Physiol (January 6, 2006). doi:10.1152/ajplung.00441.2005
Pneumocystis carinii Infection Sensitizes the Lung to Radiation-Induced Injury after Syngeneic Marrow Transplantation: Role of CD4+ T-Cells By Lauren Bruckner1, Francis Gigliotti2, Terry Wright 2, Allen Harmsen3, Robert H. Notter4, Patricia Chess4, Zhengdong Wang4, and Jack Finkelstein4. Divisions of 1Hematology/Oncology/BMT, 2Infectious Diseases, and 4Neonatology, Departments of 1,2,4 Pediatrics and of 2Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; and 3Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana, 59717.
Running title: CD4+ T cells in lung injury after Pc infection and TBI
Corresponding author: Lauren Bruckner, M.D. Department of Pediatrics, Box 850 (MRBX) Division of Hematology/Oncology University of Rochester Medical Center, 601 Elmwood Ave. Rochester, NY 14642 (585) 275-2981 phone, (585) 273-1039 fax E-mail:
[email protected]
1 Copyright © 2006 by the American Physiological Society.
Abstract A murine model of bone marrow transplant-related (BMT) lung injury was developed to study how infection sensitizes the lung to the damaging effects of total body irradiation (TBI) at doses of each that do not cause injury when given alone. Mice infected with Pneumocystis carinii (Pc) exhibited an asymptomatic, rapid, and transient influx of eosinophils and T cells in bronchoalveolar lavage fluid (BALF). In contrast, mice infected with Pc seven days prior to receiving TBI and syngeneic BMT (Pc/TBI mice) exhibited severe pulmonary dysfunction, surfactant aggregate depletion, and surfactant activity reductions at 17 days post-BMT.
BALF from Pc/TBI mice contained a
disproportionate initial influx of CD4+ T-cells (CD4+:CD8+ ratio of 2.7) that correlated with progressive lung injury (from 8 to 17 days post-BMT).
Levels of TNF-
in BALF were
significantly increased in Pc/TBI mice compared to mice given either insult alone (P
