Objective: Postischemic reperfusion of the lung triggers proinflammatory responses that stimulate injurious neutrophil chemotaxis. We hypothesized that T lymphocytes are recruited and activated during reperfusion and mediate subsequent neutrophil-induced lung ischemia-reperfusion injury. Methods: An in vivo mouse model of lung ischemia-reperfusion injury was used. C57BL/6 mice were assigned to either the sham group (left thoracotomy) or 7 study groups that underwent 1-hour left hilar occlusion followed by 1 to 24 hours of reperfusion. After in vivo reperfusion, the lungs were perfused ex vivo with buffer whereby pulmonary function was assessed. Lung vascular permeability, edema, neutrophil accumulation, and cytokine/chemokine production (tumor necrosis factor α, interleukin 17, CCL3, and CXCL1) were assessed based on Evans blue dye leak, wet/dry weight ratio, myeloperoxidase level, and enzyme-linked immunosorbent assay, respectively. Results: A preliminary study showed that 2 hours of reperfusion resulted in greater pulmonary dysfunction than 1 or 24 hours of reperfusion. The 2-hour reperfusion period was thus used for the remaining experiments. Comparable and significant protection from ischemia-reperfusion injury-induced lung dysfunction and injury occurred after antibody depletion of neutrophils or CD4+ T cells but not CD8+ T cells (P < .05 vs immunoglobulin G control). Lung ischemia-reperfusion injury was proportional to the infiltration of neutrophils but not T cells. Moreover, pulmonary neutrophil infiltration and the production of CXCL1 (KC) were significantly diminished by CD4+ T-cell depletion but not vice versa. Conclusions: Both CD4+ T lymphocytes and neutrophils accumulate during reperfusion and contribute sequentially to lung ischemia-reperfusion injury. The data suggest that neutrophils mediate ischemia-reperfusion injury; however, CD4+ T cells play a critical role in stimulating chemokine production and neutrophil chemotaxis during ischemia-reperfusion injury.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine