Doherty D E, Zagarella L, Henson P M, Worthen G S
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
J Immunol. 1989 Dec 1;143(11):3673-9.
The effects of the LPS moiety of endotoxin on monocyte adherence to an endothelial cell surface were investigated over times before the development of well described LPS-induced endothelial cell surface adhesive molecules. In an in vitro microtiter adherence assay, LPS in concentrations of 10 ng/ml to 10 micrograms/ml incubated for 20 to 60 min with human monocytes significantly stimulated monocyte adherence to human umbilical vein endothelial cell monolayers (HUVEC) and serum-coated plastic surfaces. The time course and concentration dependence of LPS-stimulated monocyte adherence to glutaraldehyde-fixed HUVEC did not differ significantly from that to unfixed HUVEC or serum-coated plastic surfaces. Pretreatment studies suggested that LPS acted on the monocyte within 25 min to stimulate adherence to untreated endothelial cells but required a minimum of 1.5 to 2 h to render the endothelial cell more adhesive for untreated monocytes. The potential role of TNF-alpha, IL-1 alpha, and IL-1 beta in this system was assessed by determining the ability of these cytokines (+/- cytokine antibodies) to increase monocyte adherence. TNF, but neither IL-1, stimulated early monocyte adherence (1 h). This TNF-stimulated monocyte adherence was abrogated by coincubation with anti-rTNF-alpha polyclonal antibody. However, the anti-rTNF antibody had no effect on LPS-induced monocyte adherence to endothelial cells or serum-coated plastic surfaces. An early action of LPS on the monocyte to induce adherence to endothelial cell surfaces may contribute to the initial localization of peripheral blood monocytes in tissues during endotoxemia. The later effects of LPS on the endothelial cell to stimulate monocyte adherence may then amplify these initial monocyte-endothelial cell interactions to prolong and intensify monocyte adherence prior to migration into tissues.
在内毒素的脂多糖（LPS）部分诱导内皮细胞表面出现众所周知的黏附分子之前，研究了LPS对单核细胞黏附于内皮细胞表面的影响。在体外微量滴定黏附试验中，浓度为10 ng/ml至10 μg/ml的LPS与人单核细胞孵育20至60分钟，可显著刺激单核细胞黏附于人脐静脉内皮细胞单层（HUVEC）和血清包被的塑料表面。LPS刺激的单核细胞黏附于戊二醛固定的HUVEC的时间进程和浓度依赖性与未固定的HUVEC或血清包被的塑料表面相比，无显著差异。预处理研究表明，LPS在25分钟内作用于单核细胞以刺激其黏附于未处理的内皮细胞，但至少需要1.5至2小时才能使内皮细胞对未处理的单核细胞更具黏附性。通过测定这些细胞因子（±细胞因子抗体）增加单核细胞黏附的能力，评估了肿瘤坏死因子-α（TNF-α）、白细胞介素-1α（IL-1α）和白细胞介素-1β（IL-1β）在该系统中的潜在作用。TNF可刺激早期单核细胞黏附（1小时），而IL-1则无此作用。与抗rTNF-α多克隆抗体共同孵育可消除TNF刺激的单核细胞黏附。然而，抗rTNF抗体对LPS诱导的单核细胞黏附于内皮细胞或血清包被的塑料表面无影响。LPS对单核细胞的早期作用以诱导其黏附于内皮细胞表面，可能有助于内毒素血症期间外周血单核细胞在组织中的初始定位。LPS随后对内皮细胞的作用以刺激单核细胞黏附，可能会放大这些初始的单核细胞-内皮细胞相互作用，从而在单核细胞迁移到组织之前延长并增强单核细胞的黏附。
