Cardiac surgery is known to trigger a systemic inflammatory response. While the use of conventional cardiopulmonary bypass (CPB) results in profound inflammation, modified mini-CPB is considered less harmful. We evaluated the impact of cardiac surgery on the expression of CD162, CD166, CD195 molecules and their association with the type of CPB used.
Methods and Results:
Twenty-four patients were enrolled in our study. Twelve of them were operated using conventional CPB while the other twelve patients underwent surgery with mini-CPB. Blood samples were analysed by flow cytometry. We observed a significant increase in median fluorescence intensity of CD162 and CD195 that peaked instantly after surgery and normalized to the baseline value on the 1st day post surgery, whereas CD166 was initially down-regulated and its median fluorescence intensity (MFI) value increased to the baseline in the next few days.
Conclusion:
We observed immediate changes in the expression of CD162, CD166, and CD195 molecules on the neutrophils after surgery in both study groups of patients. The intensity of the observed changes was significantly greater in the group of patients who underwent conventional CPB compared to patients who underwent mini-CPB cardiac surgery.
McBrideWTMcBrideSJ.The balance of pro- and anti-inflammatory cytokines in cardiac surgery. Curr Opin Anaesth1998; 11: 15–22.
2.
Rangel-FraustoMSPittetDCostiganM. The natural history of the systemic inflammatory response syndrome (SIRS): a prospective study. JAMA1995; 273: 117–123.
3.
SablotzkiAMannVSimmA. Changes in the cytokine network through escalating SIRS after heart surgery. Anaesthesiol Intensivmed Notfamed Scherzther2001; 36: 552–556.
4.
MayadasTNCullereXLowellCA.The multifaceted functions of neutrophils. Annu Rev Pathol2014; 9: 181–218.
5.
MarsikCMayrFCardonaF. Endotoxin down-modulates P-selectin glycoprotein ligand-1 (PSGL-1, CD162) on neutrophils in humans. J Clin Immunol2004Jan; 24: 62–65.
6.
OzerlatI. ALCAM as a prognostic marker for acute ischemic stroke. Nat Rev Neurol 201; 7: 474.
7.
SchröderCPiersonRNNguyenBN. CCR5 blockade modulates inflammation and alloimmunity in primates. J Immunol2007; 179: 2289–2299.
8.
PouyaniTSeedB.PSGL-1 recognition of P-selectin is controlled by a tyrosine sulfation consensus at the PSGL-1 amino terminus. Cell1995; 83: 333–343.
9.
MayadasTNJohnsonRCRayburnH. Leukocyte rolling and extravasation are severely compromised in P-selectin-deficient mice. Cell1993; 74: 541–554.
10.
HidariKIWeyrichASZimmermanGA. Engagement of P-selectin glycoprotein ligand-1 enhances tyrosine phosphorylation and activates mitogen-activated protein kinases in human neutrophils. J Biol Chem1997; 272: 28750–28756.
11.
BaXChenCGaoY. Signalling function of PSGL-1 in neutrophil: tyrosine-phosphorylation-dependent and c-Abl-involved alteration in the F-actin-based cytoskeleton. J Cell Biochem2005; 94: 365–373.
12.
GuyerDAMooreKLLynamEB. P-selectin glycoprotein ligand-1 (PSGL-1) is a ligand for L-selectin in neutrophil aggregation. Blood1996; 88: 2415–2421.
13.
YagoTShaoBMinerJJ. E-selectin engages PSGL-1 and CD44 through a common signalling pathway to induce integrin alphaLbeta2-mediated slow leukocyte rolling. Blood2010; 116: 485–494.
14.
IhnenMKöhlerNKerstenJF. Expression levels of activated leukocyte cell adhesion molecule (ALCAM/CD166) in primary breast carcinoma and distant breast cancer metastases. Dis Markers2010; 28: 71–78.
15.
WeidleUHEggleDKlostermannSSwartGW.ALCAM/CD166: cancer-related issues. Cancer Genomics Proteomics2010; 7: 231–243.
16.
JezierskaAMatysiakWMotylT.ALCAM/CD166 protects breast cancer cells against apoptosis and autophagy. Med Sci Monit2006; 12: BR263–273.
17.
GilsanzASánchez-MartínLGutiérrez-LópezMD. ALCAM/CD166 adhesive function is regulated by the tetraspanin CD9. Cell Mol Life Sci2013; 70: 475–493.
18.
SwartGW.Activated leukocyte cell adhesion molecule (CD166/ALCAM): developmental and mechanistic aspects of cell clustering and cell migration. Eur J Cell Biol2002; 81: 313–321.
19.
IolyevaMKaramanSWillrodtAH. Novel role for ALCAM in lymphatic network formation and function. FASEB J2013; 27: 978–990.
20.
CayrolRWosikKBerardJL. Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nat Immunol2008; 9: 137–145.
21.
RaportCJGoslingJSchweickartVL. Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1β, and MIP-1α. J Biol Chem1996; 271: 17161–17166.
22.
GrommesJDrechslerMSoehnleinO.CCR5 and FPR1 mediate neutrophil recruitment in endotoxin-induced lung injury. J Innate Immun2014; 6: 111–116.
23.
RottmanJBGanleyKPWilliamsK. Cellular localization of the chemokine receptor CCR5: correlation to cellular targets of HIV-1 infection. Am J Pathol1997; 151: 1341–1351.
24.
ChuangJYYangWHChenHT. CCL5/CCR5 axis promotes the motility of human oral cancer cells. J Cell Physiol2009; 220: 418–426.
van BovenWJGerritsenWBZanenP. Pneumoproteins as a lung-specific biomarker of alveolar permeability in conventional on-pump coronary artery bypass graft surgery vs mini-extracorporeal circuit: a pilot study. Chest2005; 127: 1190–1195.
27.
CurtisNVohraHAOhriSK: Mini extracorporeal circuit cardiopulmonary bypass system: a review. Perfusion2010; 25: 115–124.
28.
HamanoKKawamuraTGohraH. Stress caused by minimally invasive cardiac surgery versus conventional cardiac surgery: incidence of systemic inflammatory response syndrome. World J Surg2001; 25: 117–121.
29.
RanucciMIsgròG: Minimally invasive cardiopulmonary bypass: does it really change the outcome?Crit Care2007; 11: R45.
30.
KiaiiBFoxSSwinamerSARaymanR. The early inflammatory response in a mini-cardiopulmonary bypass system: a prospective randomized study. Innovations (Phila)2012; 7: 23–32.
31.
OhataTMitsunoMYamamuraM. Beneficial effects of mini-cardiopulmonary bypass on hemostasis in coronary artery bypass grafting: analysis of inflammatory response and hemodilution. ASAIO J2008; 54: 207–209.
32.
NguyenBAFiorentinoFReevesBC. Mini bypass and proinflammatory leukocyte activation: a randomized controlled trial. Ann Thorac Surg2016; 101: 1454-1463.
33.
FarnetiPASbranaSSpillerD. Reduction of blood coagulation and monocyte-platelet interaction following the use of a minimal extracorporeal circulation system (Synergy) in coronary artery bypass grafting (CABG). Perfusion2008; 23: 49–56.
34.
MarsikCMayrFCardonaF. Endotoxin down-modulates P-selectin glycoprotein ligand-1 (PSGL-1, CD162) on neutrophils in humans. J Clin Immunol2004; 24: 62–65.
35.
DavenpeckKLBrummetMEHudsonSA. Activation of human leukocytes reduces surface P-selectin glycoprotein ligand-1 (PSGL-1, CD162) and adhesion to P-selectin in vitro. J Immunol2000; 165: 2764–2772.
36.
StampfussJJCensarekPFischerJW. Complete downmodulation of P-selectin glycoprotein ligand in monocytes undergoing apoptosis. Arterioscler Thromb Vasc Biol2008; 28: 1375–1378.
37.
AlmulkiLNodaKAminiR. Surprising up-regulation of P-selectin glycoprotein ligand-1 (PSGL-1) in endotoxin-induced uveitis. FASEB J2009; 23: 929–939.
38.
HansenAGFreemanTJArnoldSA. Elevated ALCAM shedding in colorectal cancer correlates with poor patient outcome. Cancer Res2013; 73: 2955–2964.
39.
SwobodaSGruettnerJLangS. Hypothermia inhibits expression of CD11b (MAC-1) and CD162 (PSGL-1) on monocytes during extracorporeal circulation. In Vivo2013; 27: 459–464.
40.
MaLWangJLinJ. Cluster of differentiation 166 (CD166) regulated by phosphatidylinositide 3-kinases (PI3K)/AKT signaling to exert its anti-apoptotic role via Yes associated protein (YAP) in liver cancer. J Biol Chem2014; 289: 6921-6933.
41.
SmithJRChippsTJIliasH. Expression and regulation of activated leukocyte cell adhesion molecule in human retinal vascular endothelial cells. Exp Eye Res2012; 104: 89–93.
42.
LevesqueMCHeinlyCSWhichardLP. Cytokine-regulated expression of activated leukocyte cell adhesion molecule (CD166) on monocyte-lineage cells and in rheumatoid arthritis synovium. Arthritis Rheum1998; 41: 2221–2229.
43.
YangDZengYTianC. Transcriptomic analysis of mild hypothermia-dependent alterations during endothelial reperfusion injury. Cell Physiol Biochem2010; 25: 605–614.
44.
ReichelCAKhandogaAAndersHJ. Chemokine receptors Ccr1, Ccr2, and Ccr5 mediate neutrophil migration to postischemic tissue. J Leukoc Biol2006; 79: 114–122.
45.
HartlDKrauss-EtschmannSKollerB. Infiltrated neutrophils acquire novel chemokine receptor expression and chemokine responsiveness in chronic inflammatory lung diseases. J Immunol2008; 181: 8053–8067.
46.
ArielAFredmanGSunYP. Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Nat Immunol2006; 7: 1209–1216.
47.
YangYFTomuraMIwasakiM. IFN-alpha acts on T-cell receptor-triggered human peripheral leukocytes to up-regulate CCR5 expression on CD4+ and CD8+ T cells. J Clin Immunol2001; 21: 402–409.
48.
YangYFTomuraMIwasakiM. IL-12 as well as IL-2 upregulates CCR5 expression on T cell receptor-triggered human CD4+ and CD8+ T cells. J Clin Immunol2001; 21: 116–125.
49.
MiyaharaTRungeSChatterjeeA. D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury. FASEB J2013; 27: 2220–2232.
50.
KunesPMandakJHarrerJ. Up-regulation of the Apo/Fas (CD95) complex on neutrophils harvested during cardiac surgery: distinct findings in patients operated on with or without the use of cardiopulmonary bypass. Perfusion2010; 25: 41–46.
51.
De SomerFFrançoisKvan OeverenW. Phosphorylcholine coating of extracorporeal circuits provides natural protection against blood activation by the material surface. Eur J Cardiothorac Surg2000Nov; 18: 602–606.
52.
HsuLC.Heparin-coated cardiopulmonary bypass circuits: current status. Perfusion2001; 16: 417–428.
53.
MiholicJHudecMDomanigE. Risk factors for severe bacterial infections after valve replacement and aortocoronary bypass operations: analysis of 246 cases by logistic regression. Ann Thorac Surg1985; 40: 224–228.
54.
GovenderMBihariSDixonDL.Risk factors for prolonged mechanical ventilation after cardiopulmonary bypass for open-heart surgery in adults. Clin Res Pulmonol2015; 3: 1033.
55.
LindholmLWesterbergMBengtssonAEkrothRJensenEJeppssonA.A closed perfusion system with heparin coating and centrifugal pump improves cardiopulmonary bypass biocompatibility in elderly patients. Ann Thorac Surg2004; 78: 2131–2138; discussion 2138.
