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Expression of chemokine receptors CXCR1 and CXCR2 during cardiopulmonary bypass

Lookup NU author(s): Dr Ahmed Chishti, Professor John Dark, Dr Patrick Kesteven, Dr Hazel Powell, Dr Christopher Snowden, Dr Brian Shenton, Professor John Kirby, Dr Simon Baudouin

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Abstract

Objective: This study investigated the effects of cardiopulmonary bypass on neutrophil expression of chemokine receptors, CXCR1 and CXCR2, and the β2 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.


Publication metadata

Author(s): Kirby JA; Dark JH; Shenton BK; Baudouin SV; Chishti AD; Kesteven P; Powell H; Snowden C

Publication type: Article

Publication status: Published

Journal: Journal of Thoracic and Cardiovascular Surgery

Year: 2001

Volume: 122

Issue: 6

Pages: 1162-1166

ISSN (print): 0022-5223

ISSN (electronic): 1097-685X

Publisher: Mosby, Inc.

URL: http://dx.doi.org/10.1067/mtc.2001.116559

DOI: 10.1067/mtc.2001.116559

PubMed id: 11726891


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