Neutrophil-platelet interactions in sepsis

Introduction: Platelet-neutrophil interactions may contribute to impaired microvascular blood flow in septic shock. Methods: We studied 10 patients with severe sepsis and septic shock (SS), 8 critically ill non infected patients (CINS), and 7 healthy control (C) subjects. White blood cells (WBC) and red blood cells (RBC) were isolated from whole blood and were reconstituted in different combinations using WBC at a concentration of 9×10³mm³, RBC at hematocrit of 25% and platelet poor plasma (PPP) or platelet rich plasma (PRP). Cell suspensions were infused at 1 ml/sec through 5u pore filters. The maximal inflection point of the pressure-time curve, Pi (mm Hg) , is an index of the relative resistance of the cell suspension to filtration. Platelet activation and platelet- neutrophil interactions were assessed using monoclonal antibodies (MoAb) to CD41 and activated CD62 platelet receptors. The intensity of MoAb immunoflourescence of the leukocyte subgroup was used as an index of platelet-neutrophil adhesion. Data are expressed as mean ± standard error, * p<0.05 vs. PPP. Results: Pi (mm Hg) RBC+PPP RBC+PRP WBC+PPP WBC+PRP RBC+WBC+PPP RBC+WBC+PRP C 6.9±0.8 8.1±0.6 11.7±1.4 16.0±1.6 14.7±1.1 19.0±0.9 CINS 8.3±2.2 10.9±1.8 13.1±1.3 16.7±1.4 19.6±1.3 24.7±1.7 * S/SS 12.4±1.3 15.3±1.4 19.7±2.5 33.1±3.6 * 23±2.7 40.8±3.9 * In patients with SS, platelets were significantly activated compared to CINS or C(mean fluorescence 39.0±9.0 vs. 18.7±4.0 and 17.1±2.3 respectively, p<0.05). Similarly, platelet- neutrophil interactions were also significantly greater in patients with SS as compared to C patients (mean fluorescence 44.7± 3.6 vs. 23.0±4.1, p<0.05). Conclusion: In SS, the addition of platelets to neutrophiis significantly increases resistance to cell filtration. In contrast, the addition of platelets to RBC's does not appear to effect filtration pressure. Increased platelet activation and neutrophil-platelet interactions may impair microvascular flow in septic shock.