Lysosome-associated membrane proteins h-LAMP1 (CD107a) and h-LAMP2 (CD107b) are activation-dependent cell surface glycoproteins in human peripheral blood mononuclear cells which mediate cell adhesion to vascular endothelium

Lysosome-associated membrane proteins h-LAMP1 (CD107a) and h-LAMP2 (CD107b) are activation-dependent cell surface glycoproteins in human peripheral blood mononuclear cells which mediate cell adhesion to vascular endothelium
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DOI:
10.1006/cimm.1996.0167
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发表时间:
1996-07-10
影响因子:
4.3
通讯作者:
Holcombe, RF
Holcombe, RF
中科院分区:
医学4区
文献类型:
--
作者:
Kannan, K;Stewart, RM;Holcombe, RF

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溶酶体相关膜蛋白(Lysosome-associated membrane proteins,LAMP)是一种跨膜溶酶体糖蛋白,可在硬皮病和系统性红斑狼疮患者的淋巴细胞表面检测到。虽然这些蛋白质已被证明介导的肿瘤细胞粘附到血管内皮选择素,在外周血淋巴细胞的细胞表面上表达的LAMP的功能还没有以前检查。在本研究中,lamp 2(CD 107 b)在淋巴细胞粘附血管内皮细胞的作用和影响lamp 1(CD 107 a)和lamp 2(CD 107 b)在体外细胞表面表达的因素进行了检查。新鲜分离的PBMC和培养物中未刺激的PBMC具有低水平的细胞表面lamp 1和lamp 2表达,其在PHA刺激后显著增加(P < 0.0001)。确定了对PHA的剂量依赖性反应和不同浓度血清的作用。动力学分析表明,大多数灯1和灯2的增加发生在第一个2小时的孵育和PBMC的一个子集保持表达至少96 hr. Incubation的细胞与秋水仙碱和放线菌酮修改这些蛋白质的细胞表面表达。白细胞介素2,4,6和8只有适度的影响,对细胞表面lamp 1和lamp 2的表达程度,虽然他们显着影响不同亚型的淋巴细胞之间的表达分布。在本研究中使用的条件下,细胞表面LAMP表达主要限于CD 56(+)细胞和CD 3(+)细胞。利用基于荧光的粘附测定的功能分析显示,细胞表面lamp 2介导PBMC粘附到血管内皮,可能通过与内皮选择素相互作用。LAMP可能有助于活化的白细胞向体内炎症部位的迁移。(C)出版社:Academic Press,Inc.
Lysosome-associated membrane proteins (LAMPs) are transmembrane lysosomal glycoproteins which are detectable at the cell surface of lymphocytes in patients with scleroderma and systemic lupus erythematosus. While these proteins have been shown to mediate adhesion of tumor cells to vascular endothelial selectins, the function of LAMPs expressed at the cell surface of peripheral blood lymphocytes has not been previously examined. In the present study, the role of lamp2 (CD107b) in lymphocyte adhesion to vascular endothelium and the factors which influence in vitro cell surface expression of both lamp1 (CD107a) and lamp2 (CD107b) are examined. Freshly isolated PBMCs and unstimulated PBMCs in the culture had low levels of cell surface lamp1 and lamp2 expression which were significantly increased following PHA stimulation (P < 0.0001). A dose-dependent response to PHA and the effect of varying concentrations of serum were defined. Kinetic analysis revealed that the majority of the increase in both lamp1 and lamp2 occurred within the first 2 hr of incubation and that a subset of PBMCs maintained expression for at least 96 hr. Incubation of cells with colchicine and cycloheximide modified the cell surface expression of these proteins. Interleukins 2, 4, 6, and 8 had only a modest effect on the degree of cell surface lamp1 and lamp2 expression, though they did significantly affect the distribution of expression among different subtypes of lymphoid cells. Under the conditions utilized in this study, cell surface LAMP expression was confined primarily to CD56(+) cells and to CD3(+) cells. Functional analysis utilizing a fluorescence-based adhesion assay revealed that cell surface lamp2 mediates adhesion of PBMCs to vascular endothelium, possibly by interacting with endothelial selectins. LAMPs likely contribute to the migration of activated leukocytes to sites of inflammation in vivo. (C) 1996 Academic Press, Inc.