Luscinskas F W, Kiely J M, Ding H, Obin M S, Hébert C A, Baker J B, Gimbrone M A
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
J Immunol. 1992 Sep 15;149(6):2163-71.
We have previously reported that cytokine- or LPS-activated human umbilical vein endothelial cell (HUVEC) monolayers secrete IL-8 that can act as a neutrophil-selective adhesion inhibitor. In our study we investigated the mechanisms involved in the leukocyte adhesion inhibitory action of IL-8. The leukocyte adhesion inhibitory effect appears to be mediated by the action of IL-8 on the neutrophil, does not involve down-regulation of relevant endothelial adhesion molecules such as endothelial-leukocyte adhesion molecule-1 or intercellular adhesion molecule-1, and is quantitatively similar in different endothelial activation states that are predominantly endothelial-leukocyte adhesion molecule-1 dependent or intercellular adhesion molecule-1 dependent. In addition to inhibiting the attachment of freshly isolated peripheral blood neutrophils to cytokine-activated HUVEC monolayers, IL-8 also promoted a rapid detachment of tightly adherent neutrophils from activated HUVEC, and abolished neutrophil transendothelial migration. Certain other chemoattractants, including FMLP and C5a, had similar inhibitory actions, indicating IL-8 was not unique in its ability to inhibit various neutrophil-endothelial interactions. In contrast, two other neutrophil agonists 1-0-alkyl-2-acetyl sn-glycero-3-phosphocholine and granulocyte-macrophage-CSF, which, like IL-8, are produced by activated HUVEC, as well as the leukocyte-derived chemoattractant leukotriene B4, exerted minimal inhibitory effects on adhesion. Regardless of their ability to modulate neutrophil-endothelial cell adhesion, all these agents induced altered leukocyte surface expression of functionally important adhesion molecules, including loss of L-selectin (leukocyte adhesion molecule-1, LECAM-1) and increase in CD11b/CD18. Thus, although the above agonists have been characterized primarily as chemoattractants, our findings demonstrate that these agents can exert a wide range of modulatory effects on neutrophil-endothelial adhesive interactions.
我们之前曾报道，细胞因子或脂多糖激活的人脐静脉内皮细胞（HUVEC）单层分泌的白细胞介素-8（IL-8）可作为中性粒细胞选择性黏附抑制剂。在我们的研究中，我们调查了IL-8白细胞黏附抑制作用所涉及的机制。白细胞黏附抑制作用似乎是由IL-8对中性粒细胞的作用介导的，不涉及下调相关内皮黏附分子，如内皮细胞白细胞黏附分子-1或细胞间黏附分子-1，并且在主要依赖内皮细胞白细胞黏附分子-1或细胞间黏附分子-1的不同内皮激活状态下，其数量相似。除了抑制新鲜分离的外周血中性粒细胞与细胞因子激活的HUVEC单层的黏附外，IL-8还促进紧密黏附的中性粒细胞从激活的HUVEC上快速脱离，并消除中性粒细胞跨内皮迁移。某些其他趋化因子，包括N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）和C5a，具有类似的抑制作用，表明IL-8在抑制各种中性粒细胞-内皮相互作用的能力方面并非独一无二。相比之下，另外两种中性粒细胞激动剂1-0-烷基-2-乙酰-sn-甘油-3-磷酸胆碱和粒细胞-巨噬细胞集落刺激因子，它们与IL-8一样由激活的HUVEC产生，以及白细胞衍生的趋化因子白三烯B4，对黏附的抑制作用极小。无论它们调节中性粒细胞-内皮细胞黏附的能力如何，所有这些试剂都会诱导功能重要的黏附分子在白细胞表面的表达发生改变，包括L-选择素（白细胞黏附分子-1，LECAM-1）的丢失和CD11b/CD18的增加。因此，尽管上述激动剂主要被表征为趋化因子，但我们的研究结果表明，这些试剂可对中性粒细胞-内皮黏附相互作用产生广泛的调节作用。
