Mechanisms of platelet-neutrophil interactions in sepsis

Introduction: Platelet-neutrophil (P-PMN) interactions may contribute to impaired microvascular blood flow in severe sepsis (S). We examined whether blocking adhesive molecules mediating P-PMN interactions attenuates S induced P-PMN interactions. Methods: P's, PMN's, and normal platelet poor plasma (NPPP) were isolated from 12 normal subjects. Platelet poor plasma was isolated from 12 patients with S (SPPP). Blocking monoclonal antibodies (mAb) were added to desired cell lines after incubation with SPPP and before coincubation of PMN and P. The following mAb's were used: anti-CD41 recognizes the P complex GPIIb-IIIa; anti-CD62P blocks P-selectin on P; anti-CD11a/LFA blocks ICAM 2 on PMN; anti-CD11b and anti-CD18 block receptors on PMN. Cell suspensions were infused at 1 ml/m through 5 u pore filters and the maximal point of the pressure time curve, Pi (mm Hg), was recorded. P-PMN interactions were assessed using fluorecscein conjugated mAb to activated CD63 P receptors. The mean intensity of mAb fluorescence (MF) of the PMN subgroup was used as an index of P-PMN adhesion. Data are expressed as mean ± SE,*p<0.05 vs P+PMN+SPPP; a p<0.01 vs Δ Pi SPPP-NPPP. Conclusions: In S, P-PMN interactions significantly increase resistance to cell filtration. Addition of mAb's to cell receptors on either P's or PMN's significantly decreases resistance to cell filtration by decreasing P-PMN aggregates. Results: PI(mmHg) ΔPi from SPPP(mm Hg) MF(lfu) P+PMN+NPPP 13.7±0.7*15.8±2.6 328.4±48.6*P+PMN+SPPP 29.5±2.9 858.4±122.3 P+CD41+PMN+SPPP 20.7±2.3*8.8±2.7 a 348.7+65. 7*P+CD62P+PMN+SPPP 23.5±2.8*6.7±1.0 a 474.7±70.6*P+PMN+CD11b+SPPP 22.3±3.3*7.2±1.8 a 440.9±76.6*P+PMN+CD11a/LFA+SPPP 22.2±3.3*7.3±2. 3 a 401.0±82.3*P+PMN+CD18+SPPP 20.9±1.5*9.5±2.3 a 401.3±73.5*.