Regulation of L-selectin expression by trauma-relevant cytokines

The leukocyte adhesion molecule L-selectin is important for the rolling of neutrophil granulocytes (PMN), the first step of the cascade leading to adhesion, diapedesis, and subsequent organ dysfunction. The activation of leukocytes in the posttraumatic course is assumed to be induced by different pro-inflammatory cytokines. In the present study, we investigated the effects of stimulation with pro- and anti-inflammatory cytokines on the L-selectin surface expression on PMN. Twenty patients admitted to our institution for elective operations of the lower extremities were enrolled in a prospective clinical study. For the measurement of L-selectin expression, blood was taken before the operation (0 h), as well as 24 h and 48 h postoperatively. Without and after incubation with different pro- and anti-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10), the surface expression of L-selectin was detected using an anti-L-selectin-specific antibody and flow cytometry. L-selectin surface expression without any stimulation showed a non-significant increase 48 h after the operation (63.6±6.6 ng/ml at 0 h, 95.2±10.5 ng/ml at 48 h). Stimulation with TNF-α resulted in a significant decrease of L-selectin expression at 0 h (25.6±2.7 ng/ml; p<0.05) and 24 h (18.3±2.5 ng/ml; p<0.05), but not at 48 h (39.8±4.2 ng/ml). No significant differences were observed after stimulation with IL-1β, IL-6, and IL-10 in comparison to the non-stimulated group. The study results indicate that the primary pro-inflammatory cytokine TNF-α regulates the L-selectin surface expression on PMN after surgical trauma. Therefore, a regulation of neutrophil activation on this level might be crucial in the development of posttraumatic complications.