Acute lung reactions in a rat model of post-bone marrow transplantation pneumonitis

W. F. Ward*, J. E. Moulder, B. L. Fish, A. Molteni, Leo I Gordon, J. M. Taylor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Male WAG/Rij/MCW rats, 5-7 weeks old, received total body xirradlation (TBI) of 17 Gy in 6 fractions over 3 days, followed immediately by syngeneic bone marrow transplantation (BMT). Half of the TBI/BMT animals also received cyclophosphamide (CTX, 45 mg/kg body wt, i.p.) on the 9th and 8th days before BMT. High resolution CT (HRCT) of the thorax was performed 1 day before autopsy at 3 or 5 weeks after BMT. Compared to intact age-matched controls, TBI/BMT rats exhibited a significant and time-dependent increase in lung prostacyclin (PGI2) and thromboxane (TXA2) production. At both 3 and 5 weeks, the lungs produced more TXA2 than PGI2, a reversal of the normal ratio. Animals receiving CTX exhibited a reduction in lung angiotensin converting enzyme activity at 3 weeks (but not at 5 wks), and a 2-fold increase in PGI2 (but not TXA2) production by 5 weeks compared to those given TBI/BMT alone. Light microscopy of the lungs revealed perivascular inflammation and increased deposition of collagen in the adventitia of small arteries and arterioles, thickened alveolar septa, and focal increases in intraalveolar macrophages and erythrocytes. The latter correlated temporally with marked thrombocytopenia in the BMT animals. This histopathology was more severe in CTX-treated rats, particularly at 3 weeks after BMT, a finding confirmed by HRCT.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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