title: Post-reperfusion changes of monocyte function in coronary blood after extracorporeal circulation.
abstract: 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)-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-alpha).
  
  
  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-alpha (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-1beta 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-alpha 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.
authors.affiliation: Laboratory of Hematology and Flow Cytometry, CNR Institute of Clinical Physiology, Massa, Italy. sbrana@ifc.cnr.it
authors.forename: Silverio
authors.initials: S
authors.lastname: Sbrana
authors.forename: Stefano
authors.initials: S
authors.lastname: Bevilacqua
authors.forename: Manuela
authors.initials: M
authors.lastname: Buffa
authors.forename: Dario
authors.initials: D
authors.lastname: Spiller
authors.forename: Maria Serena
authors.initials: MS
authors.lastname: Parri
authors.forename: Jacopo
authors.initials: J
authors.lastname: Gianetti
authors.forename: Rossella
authors.initials: R
authors.lastname: De Filippis
authors.forename: Aldo
authors.initials: A
authors.lastname: Clerico
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000096:biosynthesis; D002448:Cell Adhesion; D003326:Coronary Circulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006323:Heart Arrest / Q000097:blood; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000473:pathology*; D009504:Neutrophils / Q000166:cytology; D015539:Platelet Activation; D015424:Reperfusion; D015427:Reperfusion Injury / Q000517:prevention & control*; D016897:Respiratory Burst
chemical_list: D000954:Antigens, Surface; D007378:Interleukins