Protective function of Junctional-adhesion-molecules in the rewarming process after mild hypothermia

Objective: During circulatory arrest in aortic surgery, patients are subjected to therapeutic hypothermia to reduce the risks of ischemic injury. Infiltration of pro-inflammatory cells into the surrounding tissue represents an additional hazard to patients undergoing aortic surgery. Junctional-adhesion-molecules (JAMs) are essential for the endothelial permeability and consequent transmigration. We investigated the influence of different hypothermic cell-activation temperatures followed by rewarming to 37°C on the expression of JAM-A, and JAM-B on endothelial cells after the rewarming process.

Methods: JAM-A and -B expression was analyzed on endothelial cells (EC) under following co-culture conditions a) activated PBMC/not-activated EC b) not-activated PBMC/activated EC or c) both cell types activated. Cell activation was performed at different temperatures: 37°, 30°C and 18°C and were then rewarmed to 37°C for co-culture experiments. p < 0.05 was considered as statistically significant.

Results: Under condition b) and c) at 37°C, significant less JAM-B was expressed on endothelial cells compared to JAM-A expression levels (b: JAM-A 1.001 ± 0.079tmx vs. JAM-B 0.755 ± 0.080tmx; c: JAM-A 0.910 ± 0.034tmx vs. JAM-B 0.701 ± 0.071tmx). Significant less JAM-A and JAM-B is expressed on EC when either only EC were activated at 30°C or both cell types were activated at 30°C (b: JAM-A 0.773 ± 0.030tmx vs. JAM-B 0.815 ± 0.062tmx; c: JAM-A 0.853 ± 0.058tmx vs. JAM-B 0.855 ± 0.027tmx. The cell activation at 18°C caused in all co-culture set-ups a significant drop in JAM-A and JAM-B expression on EC compared to control.

Conclusion: Our experiment shows a significant influence of temperature on JAM expression. Our data indicate that the lower the temperature difference in the rewarming process (18°C to 37°C vs. 30°C to 37°C) is, the higher are JAMs expressed and thus the endothelial cell junction and their interaction is less disturbed. The positive modulation of JAMs in the endothelium under mild hypothermia supports the clinical affirmation to favor mild hypothermia instead of severe hypothermia.