Generation of a CD11b/c upregulating and chemotactic factor by hepatocytes of endotoxic rats--nonidentity with interleukin-8.

Generation of a CD11b/c upregulating and chemotactic factor by hepatocytes of endotoxic rats--nonidentity with interleukin-8.
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内毒素大鼠肝细胞产生 CD11b/c 上调和趋化因子——与白细胞介素 8 不一致。

DOI:
10.1097/00024382-199411000-00006
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发表时间:
1994
期刊:
Shock (Augusta, Ga.)
影响因子:
--
通讯作者:
Spitzer,JA
Spitzer,JA
中科院分区:
--
文献类型:
--
作者:
Zhang,P;Bautista,AP;Spitzer,JA

文献摘要

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为了进一步阐明与短期内毒素注射相关的中性粒细胞(PMN)重新聚集到肝脏的机制(1),我们研究了由这种内毒素诱导的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。大鼠肝细胞条件培养液对幼年大鼠外周血中中性粒细胞CD11b/c表达和趋化活性具有快速诱导和剂量依赖活性。幼稚对照组大鼠在内毒素和Kupffer细胞以及内毒素大鼠肝脏PMN的存在下培养上清液也会产生激活,但程度要小得多。在100[℃]下加热失活10分钟和在37[℃]℃下60分钟的链霉蛋白酶水解会显著降低表达活性。该活性的产生不依赖于环氧合酶产物或磷脂酶A2活性,它似乎与补体途径无关。其活性与分子质量9-12和27-32 kDa有关,不能被从1:50到1:25,600的系列稀释度的大鼠白介素8抗血清降低。结果表明,急性内毒素感染大鼠肝细胞产生一种小分子蛋白因子(或因子),可上调PMN11b/c的表达和趋化活性,与大鼠白细胞介素8似乎不同。因此,内毒素血症时肝细胞可能在调节中性粒细胞功能中发挥重要作用,并参与中性粒细胞滞留肝脏的机制。
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 novel 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 CD11 b/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.