Zhang P, Bautista A P, Spitzer J A
Louisiana State University Medical Center, Department of Physiology, New Orleans 70112, USA.
Shock. 1994 Nov;2(5):332-5. doi: 10.1097/00024382-199411000-00006.
To further clarify the mechanism of polymorphonuclear leukocyte (PMN) recruitment into the liver associated with short term endotoxin infusion (1), we investigated the effect of a noval factor generated by hepatocytes of such endotoxic rats on the expression of PMN adhesion molecules CD11b/c and chemotactic activity. Conditioned medium of hepatocytes from endotoxin-infused rats shows a fast induction and dose-dependent activity for upregulating CD11b/c expression in and chemotactic activity for blood PMN of naive rats. Supernatants of naive control rats cultured in the presence of endotoxin and Kupffer cells and liver PMNs of endotoxic rats also produce activation, but to a much lesser extent. The upregulating activity can be reduced significantly by heat inactivation at 100 degrees C for 10 min and by pronase hydrolysis at 37 degrees C for 60 min. Generation of the activity does not depend on cyclooxygenase products or phospholipase A2 activity, and it does not seem to be associated with the complement pathway. The activity is associated with molecular masses of 9-12 and 27-32 kDa and cannot be reduced by antiserum to rat interleukin-8 in serial dilutions ranging from 1:50 to 1:25,600. The results show that hepatocytes from acutely endotoxin infused rats generate a small molecular weight protein factor (or factors) that is capable of upregulating PMN 11b/c expression and chemotactic activity and is seemingly different from rat interleukin-8. Thus, hepatocytes in endotoxemia may play an important role in modulating neutrophil function and contributing to the mechanism of neutrophil sequestration into the liver.
为了进一步阐明与短期内毒素输注相关的多形核白细胞（PMN）向肝脏募集的机制（1），我们研究了这种内毒素血症大鼠肝细胞产生的一种新因子对PMN黏附分子CD11b/c表达和趋化活性的影响。内毒素输注大鼠肝细胞的条件培养基对未接触内毒素大鼠血液PMN的CD11b/c表达上调和趋化活性具有快速诱导作用且呈剂量依赖性。在内毒素和库普弗细胞存在下培养的未接触内毒素对照大鼠的上清液以及内毒素血症大鼠的肝脏PMN也会产生激活作用，但程度要小得多。通过在100℃加热灭活10分钟和在37℃用链霉蛋白酶水解60分钟，上调活性可显著降低。该活性的产生不依赖于环氧化酶产物或磷脂酶A2活性，且似乎与补体途径无关。该活性与9 - 12 kDa和27 - 32 kDa的分子量相关，并且在1:50至1:25,600的系列稀释中，抗大鼠白细胞介素-8血清不能降低其活性。结果表明，急性内毒素输注大鼠的肝细胞产生一种小分子蛋白因子（或多种因子），其能够上调PMN 11b/c表达和趋化活性，且似乎与大鼠白细胞介素-8不同。因此，内毒素血症中的肝细胞可能在调节中性粒细胞功能以及促成中性粒细胞在肝脏中滞留的机制方面发挥重要作用。
