Soluble α 2-macroglobulin receptor is increased in endotracheal aspirates from infants and children after cardiopulmonary bypass

Abstract

Cytokine dysregulation contributes to the systemic inflammatory response after cardiopulmonary bypass. Clearance of cytokine binding proteins may be important in the resolution of inflammation. Our aim was to determine whether the cytokine binding protein alpha 2 -macroglobulin and its soluble receptor were upregulated in endotracheal aspirates from infants and children undergoing cardiopulmonary bypass. Seventy tracheal aspirates were collected before and after cardiopulmonary bypass from 35 infants and children undergoing surgical correction of congenital heart defects. alpha 2 -Macroglobulin and the soluble alpha 2 -macroglobulin receptor were identified by Western blot. With the use of multi-analyte cytokine profiling, pro-inflammatory and anti-inflammatory cytokines were quantified, normalized to total protein, and expressed as ratios. Paired t tests and Wilcoxon signed-rank tests were performed between prebypass and postbypass samples. Correlations were examined among alpha 2 -macroglobulin, soluble alpha 2 -macroglobulin receptor, cytokine ratios, and the clinical variables of cardiopulmonary bypass, aortic crossclamp, and circulatory arrest times. alpha 2 -Macroglobulin increased by 50% (mean densitometry increase 82,683 +/- 184,594, P = .012), and soluble alpha 2 -macroglobulin receptor increased by 17% (mean densitometry increase 506,148 +/- 687,037, P = .0001) after cardiopulmonary bypass. The ratio of interleukin-8/interleukin-4 increased by 136% ( P = .0001), and interleukin-8/interleukin-10 increased by 102% ( P = .001). The increase in soluble alpha 2 -macroglobulin receptor was positively correlated with the ratios of interleukin-8/interleukin-4 and interleukin-8/interleukin-10. There were no statistically significant positive correlations between the increase in alpha 2 -macroglobulin or soluble alpha 2 -macroglobulin receptor and measured clinical variables. We report for the first time the upregulation of alpha 2 -macroglobulin and soluble alpha 2 -macroglobulin receptor in tracheal aspirates after cardiopulmonary bypass in infants and children. Soluble alpha 2 -macroglobulin receptor correlates with increased alpha 2 -macroglobulin and a disproportionate increase in pro-inflammatory to anti-inflammatory cytokine ratios.