Inhibitory CD200R and proapoptotic CD95/CD95L molecules on innate immunity cells are modulated by cardiac surgery

Abstract

Introduction: Cardiac surgery directly initiates a systemic inflammatory response with the activation of both cellular and humoral parts of the immune system. Exaggerated immune system activation is associated with a risk of life-threatening multi-organ dysfunction (MOD) and increased morbidity and mortality in the postoperative period. The immune system response is regulated and terminated by inhibitory mechanisms, including the regulatory membrane molecules, such as CD200R, CD95, CD95L and soluble sCD200R. Methods: We measured the expression of CD95, CD95L, CD200R and sCD200R molecules in granulocyte and monocyte populations in blood samples of 30 patients who underwent coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB). Samples collected before surgery, after surgery and in the postoperative period were analyzed by flow cytometry and ELISA. Results: We found a significant increase in the percentage of granulocytes featuring the anti-inflammatory molecule CD200R (from 5% to 17.8%) after surgery. We presume that these cells were less susceptible to apoptosis because they rarely expressed CD95 as the CD200R+CD95– granulocyte sub-population prevailed. Only a small percentage of CD200R+ granulocytes expressed simultaneously CD95 (from 0.5 to 2.06 %). This small population of CD200R+CD95+ cells decreased expression of CD200R after surgery and, thus, was likely to be a source of increased sCD200R in serum (from 96 to 294 ng/mL). Also, the expression of CD95L on CD200R+ granulocytes and CD95 on CD200R+ monocytes was affected by surgery. The percentage of CD200R+ monocytes was elevated on the 1st postoperative day (from 30.6 to 49.4 %) and dropped below the preoperative value on the 7th day after surgery (from 30.6 to 19.8 %). This population comprised mainly CD200R+CD95+ monocytes in which the enhanced expression of CD95 was found. Conclusion: Our data show that the expression of CD200R, CD95 and CD95L was influenced by cardiac surgery and imply the role of these membrane molecules in cell regulation–inhibition and apoptosis following cardiac surgery.