Walker R I, Sheil J M
Exp Hematol. 1976 Nov;4(6):329-38.
Animals compromised by irradiation or graft-versus-host reaction (GVHR) are highly sensitive to endotoxin (ET). In order to determine the causes of the increased sensitivity of compromised mice, we studied alterations of hepatic (central) and bloodborne (peripheral) ET clearance processes. We observed that increased sensitivity to ET, as determined by mortality, occurred shortly after irradiation and correlated with granulocytopenia nd thrombocytopenia rather than with impairment of liver function. The involvement of granulocytes in ET clearance was indicated by injection of 51Cr-ET suspended in whole blood. By comparison with clearance of ET injected with saline or plasma, greater amounts of 51Cr-ET were sequestered in peripheral organs than in the liver. Similar results were obtained when Cr-ET in whole blood was perfused through a rat liver. ET clearance was enhanced 50% over that seen in M-199, plasma, or platelet-rich plasma. It was also found that intestinal ET contributes to mortality of granulocytopenic-thrombocytopenic mice. This was supported by the observation that bacteriologically decontaminated, irradiated animals were eight times more resistant to challenge with ET than were conventional animals. Thus, an important aspect of increased sensitivity to ET, in comprised mice, is defective peripheral clearance.
受辐射或移植物抗宿主反应（GVHR）损害的动物对内毒素（ET）高度敏感。为了确定受损小鼠敏感性增加的原因，我们研究了肝脏（中央）和血源性（外周）ET清除过程的变化。我们观察到，以死亡率衡量，对ET的敏感性增加在辐射后不久就出现了，并且与粒细胞减少和血小板减少相关，而不是与肝功能损害相关。通过注射悬浮在全血中的51Cr-ET表明粒细胞参与了ET清除。与注射生理盐水或血浆的ET清除相比，外周器官中滞留的51Cr-ET比肝脏中的更多。当全血中的Cr-ET通过大鼠肝脏灌注时，也得到了类似的结果。ET清除比在M-199、血浆或富含血小板的血浆中增强了50%。还发现肠道ET会导致粒细胞减少-血小板减少小鼠的死亡。这一观点得到了以下观察结果的支持：经细菌净化的辐射动物对ET攻击的抵抗力是传统动物的八倍。因此，受损小鼠对ET敏感性增加的一个重要方面是外周清除缺陷。
