title: Inhibition of neutrophil apoptosis after coronary bypass operation with cardiopulmonary bypass.
abstract: BACKGROUND
  Granulocyte apoptosis is a key control process in the clearance of neutrophils from inflammatory sites, and its rate is modulated both in vitro and in vivo by a number of inflammatory mediators. In this study, we investigated the influence of cardiopulmonary bypass (CPB) on neutrophil apoptosis.
  
  
  METHODS
  Twenty patients undergoing coronary operation with CPB were studied. Patients undergoing off-pump (OP) coronary bypass and healthy subjects served respectively as stressed and normal groups. Interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha were assessed on plasma collected preoperatively, at the end of CPB, and after intervals of 4, 8, 12, and 24 hours. Neutrophil apoptosis was detected by light microscopy as well as by the annexin-V assay on postoperative samples. The polymorphonuclear leukocyte (PMN) apoptotic receptors, Fas and FasL, were studied together with the activity of caspase 3 in postoperative neutrophils.
  
  
  RESULTS
  Spontaneous apoptosis was significantly delayed in PMNs from CPB patients when compared with either the stressed or control patients. Neutrophils were activated, as indicated by increased surface expression of CD11b. Western blot analysis showed a normal expression of the apoptotic receptors Fas and FasL. Caspase 3 activity was found to be significantly reduced in neutrophils from CPB patients after 18 and 24 hours of culture. When control neutrophils were cultured in the presence of postoperative plasma from OP and CPB patients, apoptosis was significantly delayed. Depleting surgical plasma of IL-6 and IL-8 completely abolished this antiapoptotic effect.
  
  
  CONCLUSIONS
  Inflammatory mediators during CPB prolong the functional lifespan of neutrophils through modulation of apoptosis, and potentiate the inflammatory response observed after coronary bypass operation.
authors.affiliation: Department of Clinical and Experimental Medicine, Unit of Cardiac Surgery, Medical School of Catanzaro, Italy. chello@unicz.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Chello
authors.forename: Pasquale
authors.initials: P
authors.lastname: Mastroroberto
authors.forename: Angela
authors.initials: A
authors.lastname: Quirino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cuda
authors.forename: Francesco
authors.initials: F
authors.lastname: Perticone
authors.forename: Francesco
authors.initials: F
authors.lastname: Cirillo
authors.forename: Elvio
authors.initials: E
authors.lastname: Covino
mesh_terms: D000368:Aged; D017209:Apoptosis; D002315:Cardiopulmonary Bypass; D020169:Caspases / Q000378:metabolism; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000378:metabolism*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000502:physiology*; D011184:Postoperative Period; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019014:fas Receptor / Q000378:metabolism
chemical_list: D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D020169:Caspases