Expression of chemokine receptors CXCR1 and CXCR2 during cardiopulmonary bypass.
OBJECTIVE
This study investigated the effects of cardiopulmonary bypass on neutrophil expression of chemokine receptors, CXCR1 and CXCR2, and the beta2 integrin CD11b.


METHODS
Ten patients undergoing coronary artery grafting with cardiopulmonary bypass were studied. Blood samples were collected preoperatively, before bypass, at termination of bypass, and 12 to 18 hours postoperatively. In vitro studies were performed on control subjects to determine changes in the surface expression of CXCR1, CXCR2, and CD11b on stimulation with interleukin 8. Receptor expression was measured by flow cytometry. Plasma levels of interleukin 8 from the patients were determined by enzyme-linked immunoassay.


RESULTS
After bypass, CXCR2 expression fell by 66% (P <.0001) and remained low postoperatively (P <.0001). CXCR1 expression persisted at preoperative levels. CD11b expression increased significantly after bypass (P <.0001), returning to prebypass levels postoperatively. In vitro studies showed a dose-related fall of both CXCR1 (P <.0001) and CXCR2 expression (P <.0001) and a significant rise in CD11b expression (P <.0001). Plasma interleukin 8 increased significantly after bypass (P <.0001), remaining elevated 12 to 18 hours postoperatively (P =.02). Correlations between interleukin 8 levels and CXCR2 expression (P <.0001) and CD11b expression (P <.03) were demonstrated.


CONCLUSIONS
CXCR2 expression is significantly down-regulated after bypass; in contrast, CXCR1 expression remains unchanged. In addition, whereas interleukin 8 is an important determinant of both CXCR1 and CXCR2 expression in vitro, it only correlates with CXCR2 and CD11b expression in vivo. This has implications in the search for antagonists against CXC chemokines and their receptors.
Chishti
A D
AD
School of Surgical and Reproductive Sciences, Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, United Kingdom. Ahmad.Chishti@ncl.ac.uk
Dark
J H
JH
Kesteven
P
P
Powell
H
H
Snowden
C
C
Shenton
B K
BK
Kirby
J A
JA
Baudouin
S V
SV
D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D023062:Receptors, Interleukin-8A / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000378:metabolism*
D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B