Mechanisms of leukocyte distribution during sepsis: an experimental study on the interdependence of cell activation, shear stress and endothelial injury

• DOI: 10.1186/cc9322
• Publication Date: 2010-11-09T07:15:41Z
• Authors: Annette Ploppa; Volker Schmidt; Andreas Hientz; Joerg Reutershan; Helene A Haeberle; Boris Nohé
• Keywords: Lipopolysaccharides; 0301 basic medicine; Umbilical Veins; Research; Critical Care and Intensive Care Medicine; 3. Good health; 03 medical and health sciences; Sepsis; Cell Adhesion; Leukocytes; Humans; Endothelium, Vascular; Inflammation Mediators; Shear Strength; Blood Flow Velocity

Abstract Introduction This study was carried out to determine whether interactions of cell activation, shear stress and platelets at sites endothelial injury explain the paradoxical maldistribution activated leukocytes during sepsis away from local infection towards disseminated leukocyte accumulation remote sites. Methods Human umbilical venous cells (HUVEC) polymorphonuclear neutrophils (PMN) were with lipopolysaccharide 100 10 ng/ml achieve adhesion molecule patterns as have been reported hyper- hypo-inflammatory stage sepsis. To examine effects activation on leukocyte-endothelial interactions, HUVEC perfused non-activated in a parallel plate flow chamber. Adhesion expression function assessed by cytometry blocking antibodies. In subset experiments sub-endothelial matrix exposed covered account for injury. investigate these flow, all done various levels (3 0.25 dyne/cm 2 ). Leukocyte-endothelial analyzed videomicroscopy analysis covariance. Results Activation rendered increasingly dependent reduction. At normal stress, shedding L-selectin decreased 56%. Increased rolling fractions PMN low revealed impaired integrin affinity despite numerical up-regulation CD11b. On sub-maximally activated, intact became prevailing determinant adhesion. Presence platelet-covered high surface density P-selectin strongest variable When compared maximally HUVEC, increased neutrophil 2.7-fold. sub-maximal 10-fold increase observed ( P < 0.05 all). Conclusions dysfunction render susceptible alternative receptors. combination, inhibit recruitment normally endothelium favor compromised perfusion or