CD4+ T lymphocytes mediate acute pulmonary ischemia–reperfusion injury

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Presentation transcript:

CD4+ T lymphocytes mediate acute pulmonary ischemia–reperfusion injury Zequan Yang, MD, PhD, Ashish K. Sharma, MBBS, Joel Linden, PhD, Irving L. Kron, MD, Victor E. Laubach, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 137, Issue 3, Pages 695-702 (March 2009) DOI: 10.1016/j.jtcvs.2008.10.044 Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Complete blood cell counts in antibody-treated mice. A, Before hilar ligation, there was an 80% reduction in neutrophils in neutrophil-depleted mice compared with IgG control mice, a 19% reduction in lymphocytes in CD8-depleted mice, and a 26% reduction of lymphocytes in CD4-depleted mice. ∗P < .05 versus IgG control mice. B, Reperfusion caused a significant decrease in total circulating leukocytes and lymphocytes in all antibody-treated mice. However, circulating neutrophils also increased after reperfusion, but this was significant only in IgG control mice. #P < .05 versus the corresponding group in panel A. WBC, Total white blood cells. The Journal of Thoracic and Cardiovascular Surgery 2009 137, 695-702DOI: (10.1016/j.jtcvs.2008.10.044) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Myeloperoxidase (MPO) levels and leukocyte subtype infiltration into peripheral lung tissue after reperfusion. A, Myeloperoxidase levels in bronchoalveolar lavage fluid after reperfusion. ∗P < .05 versus sham mice. B, Examples of immunohistochemical staining for neutrophils, CD3+ T cells, and macrophages in the study groups. The Journal of Thoracic and Cardiovascular Surgery 2009 137, 695-702DOI: (10.1016/j.jtcvs.2008.10.044) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Effect of leukocyte subtype depletion on pulmonary function after reperfusion. Airway resistance, lung compliance, and pulmonary artery pressure were significantly improved in neutrophil-depleted and CD4+ T cell–depleted mice. No protection was observed in CD8+ T cell–depleted mice. ∗P < .05 versus sham mice. #P < .05 versus IgG control and CD8-depleted mice. The Journal of Thoracic and Cardiovascular Surgery 2009 137, 695-702DOI: (10.1016/j.jtcvs.2008.10.044) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Microvascular permeability and pulmonary edema. A, Evans blue content in lung tissue as an indicator of microvascular leak. In antibody-treated mice Evans blue content was more significantly increased in IgG control and CD8-depleted mice than in neutrophil-depleted or CD4-depleted mice. B, Lung wet/dry weight ratio, as an indicator of edema, was significantly increased in IgG control and CD8-depleted mice but not in neutrophil-depleted or CD4-depleted mice (Figure 5, B). ∗P < .05 versus sham mice. #P < .05 versus IgG control and CD8-depleted mice. The Journal of Thoracic and Cardiovascular Surgery 2009 137, 695-702DOI: (10.1016/j.jtcvs.2008.10.044) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Expression of cytokines/chemokines in bronchoalveolar lavage fluid. CCL3 (macrophage inflammatory protein 1), tumor necrosis factor α (TNF-α), interleukin 17 (IL-17), and CXCL1 (KC) levels were all significantly increased in IgG control, neutrophil-depleted, and CD8-depleted mice compared with those seen in sham mice. In CD4-depleted mice there was no significant difference in CCL3, IL-17, and CXCL1 levels compared with those seen in sham mice. CXCL1 levels in CD4-depleted mice were significantly lower than in all other antibody-treated mice. ∗P < .05 versus IgG control mice. #P < .05 versus CD8-depleted mice. †P < .05 versus neutrophil-depleted mice. The Journal of Thoracic and Cardiovascular Surgery 2009 137, 695-702DOI: (10.1016/j.jtcvs.2008.10.044) Copyright © 2009 The American Association for Thoracic Surgery Terms and Conditions