Leukocyte migration across human peritoneal mesothelial cells is dependent on directed chemokine secretion and ICAM-1 expression
Leukocyte migration across human peritoneal mesothelial cells is dependent on directed chemokine secretion and ICAM-1 expression
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DOI：
10.1046/j.1523-1755.1998.00174.x
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发表时间：
1998-12-01
影响因子：
19.6
通讯作者：
Topley, N
中科院分区：
文献类型：
--
作者：
Li, FK;Davenport, A;Topley, N
背景白细胞移入腹膜腔是腹膜透析患者腹膜炎的一个诊断特征。虽然中性粒细胞（PMN）内流是腹膜感染急性期的特征，但在整个感染期间均发生显著的单核细胞（MNC）浸润。最近的数据表明，人腹膜间皮细胞（HPMC）粘附分子的表达和趋化细胞因子的合成可能是重要的过程中。在本研究中，我们已经检查了，调节和定向分泌的趋化因子（IL-8，MCP-1和RANTES）和基底外侧顶迁移的未受刺激的白细胞跨间皮细胞单层使用体外模型，其中HPMC生长在组织培养插入物的多孔膜。单独的实验已经确定了趋化因子合成和ICAM-1表达在迁移过程中的重要性。用IL-1 β或TNF α刺激HPMC的顶端导致IL-8、MCP-1和RANTES mRNA表达和合成的时间和剂量依赖性上调。所有趋化因子的这种分泌主要进入顶室（>85%）。HPMC的顶端预刺激导致PMN和MNC跨HPMC的剂量和时间依赖性迁移。在适当浓度的多克隆IL-8抗体存在下（IL-1 β（100 pg/ml）153 +/- 12 vs抗IL-8（100 ng/ml）71 +/- 7（x10（3））PMN，N = 6，P < 0.02），以及在抗ICAM-1 F（ab β 2）片段或可溶性ICAM-1存在下，中性粒细胞迁移显著减少。在同时存在多克隆MCP-1或RANTES抗体的情况下，组成性和细胞因子刺激的单核细胞迁移显著减少。这些数据表明，HPMC合成IL-8，MCP-1和RANTES响应于炎性细胞因子。HPMC衍生的C-x-C和C-C趋化因子可能有助于腹膜炎症期间白细胞的腹膜内募集。
Background Leukocyte migration into the peritoneal cavity is a diagnostic feature of peritonitis in patients treated with peritoneal dialysis (PD). While neutrophil (PMN) influx is characteristic of the acute phase of peritoneal infection, significant mononuclear cell (MNC) infiltration, occurs throughout: the whole period of infection. Recent data suggests that human peritoneal mesothelial cell (HPMC) adhesion molecule expression and the synthesis of chemotactic cytokines may be important in the process.Methods. In the present study we have examined, the regulation and directed secretion of chemokines (IL-8, MCP-1 and RANTES) and the basolateral to apical migration of unstimulated leukocytes across mesothelial cell monolayers using an in vitro model where HPMC were grown on the porous membrane of tissue culture inserts. Separate experiments have defined the importance of chemokine synthesis and ICAM-1 expression in the transmigration process.Results. Apical stimulation of HPMC with IL-1 beta or TNF alpha resulted in a time and dose dependent up-regulation of IL-8, MCP-1 and RANTES mRNA expression and synthesis. This secretion was predominately into the apical compartment (>85%) with all chemokines. Apical pre-stimulation of HPMC resulted in a dose- and time-dependent migration of both PMN and MNC across HPMC. Neutrophil migration was significantly reduced in the presence of appropriate concentrations of polyclonal IL-8 antibody (IL-1 beta (100 pg/ml) 153 +/- 12 versus anti-IL-8 (100 ng/ml) 71 +/- 7 (x 10(3)) PMN, N = 6, P < 0.02) and in the presence of anti-ICAM-1 F(ab)'(2) fragments or soluble ICAM-1. Constitutive and cytokine stimulated mononuclear cell migration was significantly reduced in the simultaneous presence of polyclonal MCP-1 or RANTES antibody.Conclusions. These data demonstrate that HPMC synthesize IL-8, MCP-1 and RANTES in response to inflammatory cytokines. HPMC-derived C-x-C and C-C chemokines might contribute to the intra-peritoneal recruitment of leukocytes during peritoneal inflammation.