Sharar S R, Sasaki S S, Flaherty L C, Paulson J C, Harlan J M, Winn R K
Department of Anesthesiology, University of Washington School of Medicine, Seattle.
J Immunol. 1993 Nov 1;151(9):4982-8.
Adhesion molecules are responsible for PMN-endothelial cell interactions involved in both PMN-mediated endothelial injury (e.g., after ischemia-reperfusion injury) and PMN-mediated host defense against bacterial infection. Inhibition of PMN-endothelial adherence with CD18 and P-selectin mAb has been shown to ameliorate the tissue injury resulting from ischemia and reperfusion under a variety of experimental conditions. However, interference with PMN function may result in an increased risk of bacterial infection. Previous investigations suggest that CD18 blockade can lead to increased infectious risk. Little is known of the infectious risks associated with selectin blockade. We report the effects of P-selectin blockade (using mAb PB1.3) on bacteria-induced PMN emigration into the peritoneum and subcutaneous (s.c.) tissue in rabbits. Leukocyte and PMN emigration into the peritoneum 4 h after inoculation with 10 ml of 10(9) CFU/ml Escherichia coli was significant in saline-treated animals, and not different in animals pretreated with mAb PB1.3. Similarly, the incidence and severity of abscess formation 7 days after s.c. inoculation with Staphylococcus aureus (10(7), 10(8), or 10(9) CFU) was not increased in rabbits pretreated with mAb PB1.3 compared to saline. PMN emigration to the s.c. S. aureus was also similar in both saline and mAb PB1.3-treated animals, as determined by light microscopy. We conclude that P-selectin blockade with mAb PB1.3: 1) does not interfere with acute, E. coli-induced PMN emigration into the peritoneum, 2) does not increase the incidence or severity of S. aureus abscess formation in s.c. tissue, and 3) interferes less with PMN antibacterial host defense mechanisms than inhibition of CD18-mediated PMN adherence.
黏附分子负责介导多形核白细胞（PMN）与内皮细胞的相互作用，这一过程既参与PMN介导的内皮损伤（如缺血再灌注损伤后），也参与PMN介导的宿主抗细菌感染防御。在多种实验条件下，用CD18和P-选择素单克隆抗体抑制PMN与内皮细胞的黏附已被证明可改善缺血再灌注导致的组织损伤。然而，干扰PMN功能可能会增加细菌感染风险。先前的研究表明，阻断CD18可导致感染风险增加。关于选择素阻断相关的感染风险知之甚少。我们报告了用P-选择素阻断剂（使用单克隆抗体PB1.3）对兔体内细菌诱导的PMN向腹膜和皮下组织迁移的影响。用10ml含10⁹CFU/ml大肠杆菌接种4小时后，生理盐水处理组动物的白细胞和PMN向腹膜的迁移显著，而用单克隆抗体PB1.3预处理的动物与生理盐水处理组无差异。同样，与生理盐水相比，用单克隆抗体PB1.3预处理的兔在皮下接种金黄色葡萄球菌（10⁷、10⁸或10⁹CFU）7天后脓肿形成的发生率和严重程度并未增加。通过光学显微镜观察，生理盐水处理组和单克隆抗体PB1.3处理组动物的PMN向皮下金黄色葡萄球菌的迁移情况也相似。我们得出结论，用单克隆抗体PB1.3阻断P-选择素：1）不干扰急性大肠杆菌诱导的PMN向腹膜的迁移；2）不增加皮下组织金黄色葡萄球菌脓肿形成的发生率或严重程度；3）与抑制CD18介导的PMN黏附相比，对PMN抗菌宿主防御机制的干扰较小。
