Stress Induced Eosinophilpoiesis Contributes to Mortality after Pulmonary Resection

Abstract

Abstract Factors affecting mortality after lung surgery remain poorly explored. We performed pulmonary lobar resections(removing □ 1/5 of the total pulmonary volume) from C57BL/6 mice and evaluated quantitative changes in various leucocytes in the remaining lung, blood and spleen. A nearly four-fold increase in eosinophils was evident by day-7 post resection with a gradual return to baseline by day 30. Evaluation of the bone marrow demonstrated no change in common myeloid, granulocyte-monocyte or eosinophil progenitors. However the number of early stage and mature eosinophils doubled after lobar resection suggesting that pulmonary surgery augmented maturation of eosinophils. Neutralization of IL-5 decreased overall eosinophil numbers but the relative differences between resting and post-resection mice remained. Further evaluation of bone marrow demonstrated an increase in IL-25, IL-6, IL-9, KC and MCP-1 after pulmonary resection. We next performed right pneumonectomies in saline or diphtheria toxin-treated iPHIL mice, where diphtheria toxin receptor expression is limited to eosinophils, and noted a 70% mortality in eosinophil sufficient vs. 20% mortality in eosinophil depleted mice (p=.005). Severe hypoxia was noted in eosinophils sufficient vs. deficient mice (pO2 of 54.3+/−5.7 vs. 83.6+/−11.63; p=.04) four hours prior to resection. Taken together out data demonstrate that pulmonary surgery leads to bone marrow-specific maturation of eosinophils and systemic eosinophilia which directly contributes to perioperative mortality. Thus defining factors which may disrupt this process offers the opportunity to improve outcomes after lung surgery. Supported by PO1 AI116501, RO1 AI145108-01