Body to E- and L-selectin does not prevent lung injury or mortality in septic baboons
Body to E- and L-selectin does not prevent lung injury or mortality in septic baboons
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DOI：
10.1164/ajrccm.157.3.9707129
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发表时间：
1998-03-01
影响因子：
24.7
通讯作者：
Piantadosi, CA
中科院分区：
文献类型：
--
作者：
Carraway, MS;Welty-Wolf, KE;Piantadosi, CA
通过上调细胞粘附分子募集多形核白细胞（PMN）是脓毒症和急性呼吸窘迫综合征（ARDS）损伤的一种机制。我们假设，狒狒与人E-和L-选择素（EL-246）的单克隆抗体在脓毒症的预处理将减少中性粒细胞流入组织，并导致在革兰氏阴性脓毒症的器官损伤较少。我们研究了14只麻醉、通气的成年狒狒;六只动物在输注LD 100活大肠杆菌之前接受了1 mg/kg的EL-246，六只动物接受了大肠杆菌。大肠杆菌输注而不进行抗体治疗。另外两只动物静脉内接受1 mg/kg EL-246，未输注细菌。间歇性测量循环压、心输出量、尿量、动脉血气、通气：灌注比（（V）对点A/（Q）对点）和血液学状态。实验在48 h或死亡时结束。收获组织用于病理学和生物化学测量。急诊大肠杆菌输注与高动力状态、肺动脉高压、全身性低血压、尿量减少（UOP）和代谢性酸中毒有关。抗体部分阻断PMN迁移，但有几个显着的生理或生化差异EL-246治疗和未治疗的动物。在抗体处理的动物中，UOP降低，代谢性酸中毒恶化，中位生存时间显著缩短。我们的结论是，在革兰氏阴性脓毒症中使用E-和L-选择素抗体治疗不能改善气体交换或防止肺损伤，并且与灵长类动物的生存时间减少有关。
Recruitment of polymorphonuclear leukocytes (PMN) through upregulation of cellular adhesion molecules is a proposed mechanism of injury in sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that pretreatment of baboons with a monoclonal antibody to human E-and L-selectin (EL-246) during sepsis would decrease PMN influx into tissues and result in less organ injury during gram-negative sepsis. We studied 14 anesthetized, ventilated adult baboons; six animals received 1 mg/kg of EL-246 before infusion of an LD100 of live Escherichia coli and six received the E. coli infusion without antibody therapy. Two other animals received 1 mg/kg of EL-246 intravenously without an infusion of bacteria. Intermittent measurements were made of circulatory pressures, cardiac output, urine output, arterial blood gases, ventilation:perfusion ratio ((V) over dot A/(Q) over dot ), and hematologic status. The experiments were ended at 48 h or at the time of death. Tissues were harvested for pathology and biochemical measurements. The E. coli infusions were associated with a hyperdynamic state, pulmonary hypertension, systemic hypotension, decreased urine output (UOP), and metabolic acidosis. The antibody partly blocked PMN migration, but there were few significant physiologic or biochemical differences between the EL-246-treated and untreated animals. In the antibody-treated animals, UOP was decreased, metabolic acidosis was worsened, and median survival time was decreased significantly. We conclude that treatment with an antibody to E-and L-selectin in gram-negative sepsis does not improve gas exchange or protect against lung injury, and is associated with decreased survival time in primates.