Lung compartmentalization of inflammatory cells in sepsis

Lung injury commonly occurs in the setting of systemic inflammatory respons e syndrome occurring during bacterial sepsis. There has been little work qu antifying different leukocytes within the different compartments of the lun g and their association with overt lung injury in sepsis. We examined the p athogenesis of lung injury after cecal ligation and puncture (CLP), a clini cally relevant model of sepsis. To assess the sequestration and migration o f leukocytes, leukocyte differentials were obtained for the lung vascular c ompartment and the bronchoalveolar airspace. At 24 h post CLP, there were s igns of edema in the lung, while at 48 h after CLP, there were clear indica tions of alveolar wall thickening with increased cellularity and diffuse al veolar hemorrhage. The number of lymphocytes in the pulmonary vascular comp artment dropped by 50% and doubled in the (bronchoalveolar lavage) BAL, 24 h after CLP compared to sham controls suggesting that there was transendoth elial migration of lymphocytes. At 48 h after CLP, lymphocyte numbers in th e vasculature was similar to controls but BAL lymphocyte numbers were still raised. The number of pulmonary intravascular neutrophils were similar to controls at 24 h post CLP but were greatly elevated 48 h after CLP. The inc rease in neutrophils was partly due to a substantial increase in the percen tage of immature band cells, indicating recruitment of neutrophils from the bone marrow. There were very few neutrophils in the BAL of sham controls a nd CLP rats. Perfusate monocyte/macrophages were significantly increased 48 h after CLP and a similar increase in macrophages was observed in the BAL. These results strongly suggest a role for lymphocytes and macrophages in t he development of overt lung injury as the migration of these cells corresp onds to that of the appearance of lung injury 48 h after CLP. importantly o ur data also demonstrates the compartmentalization and migration of differe nt inflammatory cell-types during the development of sepsis.