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Effect and mechanism of acute graft versus host disease on early diffuse murine lung injury following allogeneic stem cell transplantation

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Abstract

To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/6→BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor α (TNFα) and Interferon (IFNγ) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFα were lower on day +7 than on day +3. In group B, the levels of TNFα attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFα were highest on day +7 and there was a significant difference between those on days +7 and +14 (P=0.816). In group A, the levels of IFNγ on day +7 were higher than on day +3. In group B, the levels of IFNγ increased progressively, but the comparison of IFNγ levels in different times had no statistical significance (P=0.521, 0.118, 0.340). In group C, the levels of IFNγ attained a peak by day +7 and decreased on day +14. aGVHD is the main cause of early non-infectious lung injury. T lymphocytes and TNFα are possibly implicated in the pathogenesis of acute GVHD-induced lung injury. The decreased levels of IFNγ in lung tissues following transplantation might be associated with pulmonary fibrosis in late non-infectious pulmonary complications.

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Authors and Affiliations

  1. Department of Hematology, Southern Hospital, Southern Medical University, Guang Zhou, 510515, China

    Juan Ning, Qi Fa Liu, Xiao Dan Luo, Zhi Ping Fan & Yu Zhang

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  1. Juan Ning
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  2. Qi Fa Liu
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  3. Xiao Dan Luo
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  4. Zhi Ping Fan
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  5. Yu Zhang
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Correspondence to Qi Fa Liu.

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Supported by the National Natural Science Foundation of China (Grant No. 30971300)

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Ning, J., Liu, Q.F., Luo, X.D. et al. Effect and mechanism of acute graft versus host disease on early diffuse murine lung injury following allogeneic stem cell transplantation. SCI CHINA SER C 52, 1016–1022 (2009). https://doi.org/10.1007/s11427-009-0139-8

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  • DOI: https://doi.org/10.1007/s11427-009-0139-8

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