Differential patterns of neutrophil adhesion molecules during cardiopulmonary bypass in humans.

BACKGROUND

Neutrophils are activated during cardiopulmonary bypass, and it is believed that they play an important role in the postoperative inflammatory response. The effects of neutrophils are mediated by the surface adhesion molecules L-selectin, beta 2-integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1), and it has been reported that beta 2-integrins are upregulated and L-selectin downregulated by cardiopulmonary bypass. However, the time course of these changes and their relative importance are unclear.

METHODS AND RESULTS

To investigate the temporal changes in the expression of the neutrophil surface adhesion molecules L-selectin, beta 2-integrins, and PECAM-1 induced by cardiopulmonary bypass, we used immunofluorescent flow cytometry in blood samples obtained at various times (before anesthesia, before bypass, and 0.25, 0.5, 1, 2, 4, 24, and 48 hours after initiation of bypass) from patients undergoing routine coronary artery bypass graft surgery. Anesthesia had no effect on the expression of any of the study molecules. The expression of all beta 2-integrins was not significantly affected during the entire study period. The mean fluorescence (expressed as a percentage of control) of CD18 did not change significantly during the first 2 hours after the initiation of cardiopulmonary bypass, but then it declined by 4 hours (P = NS) and attained its lowest values after 24 and 48 hours. The mean fluorescence of CD11b and CD11c decreased by 2 and 4 hours and remained reduced after 24 hours and 48 hours. The expression of PECAM-I decreased rapidly after the initiation of cardiopulmonary bypass to achieve 60 +/- 8% of the preanesthesia control values (P < .05) after only 1 hour; it fell to its lowest after 4 hours (44 +/- 8%; P < .05); and then it recovered partially by 24 hours (60 +/- 11%; P < .05), with a further recovery toward control after 48 hours (77 +/- 8%; P = NS). The profile for the mean fluorescence of PECAM-I was identical to that observed with its expression. In contrast, the expression and mean fluorescence of L-selectin were not changed during the 48-hour period.

CONCLUSIONS

This study has demonstrated that cardiopulmonary bypass in humans induces (1) a rapid reduction in the expression of PECAM-I of circulating neutrophils, (2) a later reduction of beta 2-intergrin activity without significant changes in their expression, and (3) no alterations in the expression and activity of L-selectin. Thus, although the mechanism for the absence of neutrophil upregulation of beta 2-integrins and downregulation of L-selectin (no activation) remains to be elucidated, the downregulation of PECAM-1 indicates an early neutrophil activation, and its inhibition may represent a target for reducing the inflammatory response usually associated with cardiopulmonary bypass.