Increased expression of toll-like receptor-2 and-4 on leukocytes from patients with sepsis
Increased expression of toll-like receptor-2 and-4 on leukocytes from patients with sepsis
复制标题
DOI：
10.1097/01.shk.0000142256.23382.5d
复制
发表时间：
2004-11-01
期刊：
影响因子：
3.1
通讯作者：
Keel, M
中科院分区：
文献类型：
--
作者：
Härter, L;Mica, L;Keel, M
脓毒症期间单核细胞或粒细胞对内毒素的反应性降低（内毒素耐受性）可能取决于Toll样受体（TLR）。在来自脓毒症患者（n = 21）或健康对照（n = 12）的中性粒细胞（PMN）和单核细胞上测量TLR-2和TLR-4的表达。将白细胞（1 × 10（6）/mL）在37 ℃下与或不与TLR-4（LPS 1 μ g/mL）或TLR-2配体（MALP-2 2 2 nM）孵育。在用特异性抗体染色后，在FACS中测定0、4和16 h时TLR-2和TLR-4的表面表达。通过ELISA测量IL-8和TNF-α的释放。从脓毒症患者新鲜分离的PMN显示TLR-2（78.0 +/-18.6）和TLR-4（11.4 +/-2.3）的平均荧光显著（P < 0.05）高于对照组（12.8 +/-2.2和2.3 +/-0.4）。类似地，来自患者的单核细胞表现出比来自对照的细胞（149.5 +/- 27.1和52.2 +/- 7.6）更高的TLR-2和TLR-4表达（300.8 +/- 40.6和92.7 +/- 12.1）。在脓毒症患者中，TLR-2和TLR-4在PMN上的表达在孵育16小时期间增加（106.2 +/- 22.1和34.5 +/- 5.3），而在对照组中保持不变（19.3 +/- 6.1和5.4 +/- 1.9）。与LPS或MALP-2孵育对来自对照或患者的细胞中TLR-4或TLR-2的表达没有影响。尽管在脓毒症患者的细胞中TLR表达增加，但内毒素诱导的TNF-α和IL-8的释放与对照中的释放没有区别。因此，脓毒症患者的内毒素耐受性不仅仅取决于TLR-2或TLR-4的表达，还涉及其他机制。
The reduced responsiveness of monocytes or granulocytes toward endotoxin (endotoxin tolerance) during sepsis may depend on Toll-like receptors (TLR). The expression of TLR-2 and TLR-4 was measured on neutrophils (PMN) and monocytes from patients with sepsis (n = 21) or healthy controls (n = 12). Leukocytes (1 x 10(6)/mL) were incubated at 37degreesC with or without a TLR-4 (LPS 1 mug/mL) or a TLR-2 ligand (MALP-2 2 nM). Surface expression of TLR-2 and TLR-4 at 0, 4, and 16 h was determined in FACS after staining with specific antibodies. The release of IL-8 and TNF-alpha was measured by ELISA. Freshly isolated PMN from patients with sepsis exhibited significantly (P < 0.05) higher mean fluorescence for TLR-2 (78.0 +/- 18.6) and TLR-4 (11.4 +/- 2.3) than controls (12.8 +/- 2.2 and 2.3 +/- 0.4). Similarly, monocytes from patients exhibited higher TLR-2 and TLR-4 expression (300.8 +/- 40.6 and 92.7 +/- 12.1) than cells from controls (149.5 +/- 27.1 and 52.2 +/- 7.6). In patients with sepsis, expression of TLR-2 and TLR-4 on PMN increased during 16 h of incubation (106.2 +/- 22.1 and 34.5 +/- 5.3), whereas it remained unchanged in controls (19.3 +/- 6.1 and 5.4 +/- 1.9). Incubation with LPS or MALP-2 had no effect on TLR-4 or TLR-2 expression in cells from either controls or patients. Despite increased TLR expression in cells from patients with sepsis, the endotoxin-induced release of TNF-a and IL-8 was indistinguishable from that in controls. Therefore, the endotoxin tolerance seen in patients with sepsis does not depend solely on TLR-2 or TLR-4 expression, and other mechanisms must be involved.