Anti-inflammatory haemoglobin scavenging monocytes are induced following coronary artery bypass surgery.
OBJECTIVE
Circulating monocytes may counter systemic pro-inflammatory and haemolytic insults through the expression and shedding of the haemoglobin scavenger receptor (CD163). This prospective study aims to assess the effects of coronary artery bypass grafting with and without cardiopulmonary bypass (CPB) on haemoglobin scavenging and anti-inflammatory monocyte behaviour.


METHODS
Forty consecutive patients underwent coronary surgery using CPB (n=20) and off-pump (n=20) techniques. Peri-operative blood samples were taken until the fifth day following surgery and statistical comparison performed to baseline using group- and subject-based analysis. Monocyte receptor expression and plasma concentrations of anti-inflammatory molecules were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively.


RESULTS
Monocyte CD163 expression was significantly elevated post-operatively in both surgical groups with (p=0.001) and without CPB (p=0.000) at 24-48h. By contrast, shed CD163 (p=0.02) and haemoglobin-haptoglobin complexes (p=0.000) in plasma were only significantly elevated in the on-pump group at 2-4h. Subject-based analysis demonstrated that CPB is an independent predictor of monocyte CD163 (p=0.002) and plasma sCD163 (p=0.01) concentration adjusting for the measurement timing. Significant downregulation of the monocyte major histocompatibility complex II receptor was observed in both surgical groups, whereas lipopolysaccharide receptor (CD14) expression only declined following on-pump surgery. The anti-inflammatory cytokine interleukin (IL)-10 was elevated post-operatively in both surgical groups peaking earlier in the on-pump group (2h) versus off-pump group (4h). The immunoregulatory IL-6 cytokine was significantly upregulated at 4h in both groups.


CONCLUSIONS
Coronary artery bypass surgery induces monocyte-associated anti-inflammatory and immunoregulatory responses. There was no significant difference in haemolysis although the effect on monocyte CD163 and plasma sCD163 concentration was significantly different between the two groups. Compensation for varying pro-inflammatory and haemolytic insults may explain the differences observed. Therapeutic strategies for inducing such desirable circulating monocytes may potentially improve surgical outcome and patient recovery.
Cardiothoracic Surgery and Cardiovascular Medicine Units, Imperial College Healthcare NHS Trust, Imperial College London, London, UK.
Pandelis
P
Philippidis
Thanos
T
Athanasiou
Imad
I
Nadra
Hutan
H
Ashrafian
Dorian O
DO
Haskard
R Clive
RC
Landis
Kenneth M
KM
Taylor
D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass / Q000009:adverse effects / Q000379:methods*; D047549:Coronary Artery Bypass, Off-Pump / Q000009:adverse effects / Q000379:methods; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000097:blood; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011184:Postoperative Period; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood*; D051116:Receptors, Scavenger / Q000097:blood*; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006454:Hemoglobins; D000949:Histocompatibility Antigens Class II; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D016753:Interleukin-10