Henseleit U, Steinbrink K, Goebeler M, Roth J, Vestweber D, Sorg C, Sunderkötter C
Institute of Experimental Dermatology Freiburg, Germany.
J Pathol. 1996 Nov;180(3):317-25. doi: 10.1002/(SICI)1096-9896(199611)180:3<317::AID-PATH670>3.0.CO;2-O.
E-selectin (CD62E, formerly termed ELAM-1) is a cytokine-inducible adhesion molecule which mediates the binding of neutrophils, monocytes, and skin homing T-cells. The murine homologue of E-selectin has been cloned. A monoclonal antibody (21KC10) was used here to study immunohistochemically the expression and regulation of murine E-selectin in vitro and in vivo. As described for the human system, there was no staining of normal endothelium in skin and other tissues. LPS and tumour necrosis factor-alpha (TNF-alpha), but not interleukin-4 (IL-4) or interferon-gamma (IFN-gamma), induced a transient expression of E-selectin, both when injected in vivo and when added to endothelial cell lines in vitro. To analyse temporal expression of E-selectin under pathophysiological conditions in vivo, we chose two murine models of inflammation: allergic (ACD) and irritant contact dermatitis (ICD). Expression of E-selectin was found to be induced on vascular endothelium of post-capillary venules in both ACD and ICD. In ICD, maximal staining of endothelial cells occurred earlier than in ACD. Expression of E-selectin during ICD and ACD was then compared between strains of mice which differ with regard to the intensity of their inflammatory reaction. BALB/c mice, which in contrast to C57BI/6 mice show a denser infiltrate and prolonged influx of granulocyte and monocytes, revealed a more pronounced and more prolonged expression of E-selectin than C57BI/6 mice. This held true for both ACD and ICD, and in each case, peak expression of E-selectin was associated with the highest density of the leukocytic infiltrate. This study thus reveals regulatory mechanisms involved in the expression of murine E-selectin in vivo and in vitro. It also demonstrates a correlation between endothelial expression of E-selectin and the genetically determined intensity of the inflammatory response.
E-选择素（CD62E，原称为ELAM-1）是一种细胞因子诱导的黏附分子，介导中性粒细胞、单核细胞和皮肤归巢T细胞的结合。E-选择素的小鼠同源物已被克隆。本文使用一种单克隆抗体（21KC10），通过免疫组织化学方法研究小鼠E-选择素在体内外的表达和调控。正如在人类系统中所描述的那样，皮肤和其他组织中的正常内皮细胞没有染色。脂多糖（LPS）和肿瘤坏死因子-α（TNF-α），而非白细胞介素-4（IL-4）或干扰素-γ（IFN-γ），在体内注射以及体外添加到内皮细胞系时，均可诱导E-选择素的短暂表达。为了分析体内病理生理条件下E-选择素的时间表达，我们选择了两种小鼠炎症模型：过敏性（ACD）和刺激性接触性皮炎（ICD）。发现在ACD和ICD中，毛细血管后微静脉的血管内皮上均诱导了E-选择素的表达。在ICD中，内皮细胞的最大染色比ACD出现得更早。然后，在炎症反应强度不同的小鼠品系之间比较了ICD和ACD期间E-选择素的表达。与C57BI/6小鼠相比，BALB/c小鼠表现出更密集的浸润以及粒细胞和单核细胞的持续流入，其E-选择素的表达比C57BI/6小鼠更明显且持续时间更长。这在ACD和ICD中均成立，并且在每种情况下，E-选择素的峰值表达都与白细胞浸润的最高密度相关。因此，本研究揭示了小鼠E-选择素在体内外表达所涉及的调控机制。它还证明了E-选择素的内皮表达与遗传决定的炎症反应强度之间的相关性。
