• Linda A Kirschenbaum, Dennis McKevitt, Melinda Rullan, Bernd Reisbeck, Tisha Fujii, and Mark E Astiz.
• Department of Medicine, New York Medical College, Valhalla, New York, USA.
• Crit. Care Med. 2004 Sep 1; 32 (9): 1904-9.

ObjectiveTo examine the role of platelets, fibrin, and adhesion molecules in mediating neutrophil-endothelial cell interactions in septic shock.DesignControlled experiments using phase contrast microscopy to examine neutrophil, platelet, and endothelial cell interactions in flowing cell suspensions under simulated physiologic conditions.SettingUniversity research laboratory.PatientsAdult patients with septic shock and normal volunteers.InterventionsMicroslides were coated with human umbilical vein endothelial cells. Neutrophils were removed from control subjects and patients in septic shock and were perfused over endothelial cells at rates representing a range of physiologic shear stresses. In an attempt to examine the effects of fibrin deposition on neutrophil-endothelial cell interactions, neutrophils, with and without platelets, were suspended in plasma and serum was removed from patients in septic shock. In addition, blocking monoclonal antibodies against the platelet receptor P-selectin and neutrophil receptor CD11b/CD18, and a platelet glycoprotein IIb/IIIa inhibitor, were incubated with cells suspended in plasma. Phase contrast video microscopy was used to count the number of neutrophils/mm adherent to endothelial cells during cessation of flow. Neutrophil rolling velocity was calculated as the time required for neutrophils to move across a 1-mm field (mm/sec). Leukoaggregation was defined as the number of neutrophils in aggregates (three or more nuclei) across a 1-mm field.Measurements And Main ResultsNormal neutrophils exposed to plasma from patients with septic shock demonstrated significant increases in aggregation and endothelial cell adherence with associated decreases in neutrophil rolling velocity. These changes were significantly enhanced in the presence of platelets and significantly attenuated in the presence of serum, which is fibrinogen depleted. Preincubation with antibodies to the surface receptors P-selectin, CD11b/CD18, and glycoprotein IIb/IIIa abrogated the changes in neutrophil aggregation, adhesion, and rolling velocity.ConclusionsThese data suggest that platelets and fibrinogen play an important role in mediating neutrophil-endothelial cell adherence in septic shock.

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