Post-reperfusion changes of monocyte function in coronary blood after extracorporeal circulation

Background: Neutrophil and mononuclear cell functional changes represent a hallmark of inflammation during cardiopulmonary bypass and cardiovascular surgery. Knowledge of mechanisms underlying monocyte functional modulation in coronary blood may be useful to develop protective interventions that can limit ischemia/reperfusion injury. Methods: Samples of 13 patients were drawn from venous coronary sinus before cardioplegic arrest and after reperfusion. The following parameters were studied: surface molecules expression (CD18, CD11b, CD44, CD162, CD15s, CD80, CD86, CD16, CD49d, CD29, CD25, HLA-DR, Toll-like receptor-4 [TLR- 4], CXCR1, CCR2, CCR5, CX3CR1), oxidative burst response, monocyte-platelet conjugates (using antibodies against CD45, CD14, CD41a), and platelet activation (CD62P, PAC-1). Enzyme-linked immunosorbent assays were performed to measure levels of interleukin (IL)-1b, IL-6, IL-8, IL-10, and tumor necrosis factor- a (TNF-a). Results: Coronary reperfusion down-modulated monocyte molecules expression, especially for CD18 (P = 0.048), CD44 (P = 0.0035), CD49d (P = 0.0029), CD29 (P = 0.032), HLA-DR (P < 0.0001), TLR-4 (P = 0.0109), CCR2 (P = 0.0184), CCR5 (P = 0.0396), and CX3CR1 (P < 0.0001). A marginal increase (P = 0.062) of a normalized adhesion index between monocytes and platelets was observed at reperfusion. No variations were detected for the monocyte oxidative burst and platelet activation. Increased levels of IL-6 (P = 0.013), TNF-a (P = 0.0272), and IL-10 (P = 0.0008) were measured after cardioplegia. Conclusions: The lack of CD11b and CD25 variations and of the oxidative burst exclude monocyte activation at reperfusion. The high after-cardioplegia level of IL-10, the decreased expression of HLA-DR and TLR-4, and the absence of IL-1b and IL-8 suggest an IL-10-mediated functional depression of monocyte, including their adhesive and migratory capacities. The lack of an after-cardioplegia orientation toward IL-10 producing a ''macrophage-like'' CD14+/CD16+ phenotype might mean that myocardial infiltrating lymphocytes are the main source of IL-10. Moreover, the increased after-cardioplegia levels of IL-6 and TNF-a might be due to myocardial and endothelial activations. The increased adhesion index between monocyte and platelets, without receptor variations, suggests a monocyte membrane modification induced by extracorporeal circulation.