IDENTIFICATION OF A HUMAN PERIPHERAL LYMPH-NODE HOMING RECEPTOR - A RAPIDLY DOWN-REGULATED ADHESION MOLECULE

IDENTIFICATION OF A HUMAN PERIPHERAL LYMPH-NODE HOMING RECEPTOR - A RAPIDLY DOWN-REGULATED ADHESION MOLECULE
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DOI:
10.1073/pnas.87.6.2244
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发表时间:
1990-03-01
影响因子:
11.1
通讯作者:
BUTCHER, EC
BUTCHER, EC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KISHIMOTO, TK;JUTILA, MA;BUTCHER, EC

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淋巴细胞向淋巴器官的迁移涉及器官特异性归巢受体。由MEL-14单克隆抗体(mAb)定义的小鼠外周淋巴结归巢受体是一种凝集素样细胞表面蛋白,在用佛波醇12-肉豆蔻酸酯13-乙酸酯激活细胞后迅速下调。我们已经提出了单克隆抗体对快速脱落的分子释放的细胞表面活化的人白细胞。五种mAb DREG-55、-56、110、-152和-200定义了参与外周淋巴结(PLN)高内皮微静脉(HEV)的人淋巴细胞识别的80-至85-kDa分子。DREG-56 mAb特异性抑制> 90%的人淋巴细胞与外周淋巴组织冷冻切片中的HEV结合,但不抑制粘膜淋巴组织。此外,gp 80抗原在能够结合PLN HEV的淋巴细胞系上表达。DREG-56 mAb还抑制淋巴细胞与来自汉逊酵母Y-2448的磷酸甘露聚糖单酯核心的结合,这是一种与人类和小鼠淋巴细胞识别PLN HEV相关的活性。最后,所有五种DREG mAb特异性染色用LAM-1 cDNA转染的COS细胞,LAM-1 cDNA是小鼠MEL-14抗原的推定人类同源物。这些结果证明DREG mAb定义了PLN HEV的人淋巴细胞归巢受体,并表明该人抗原与MEL-14定义的鼠淋巴细胞归巢受体同源。
Lymphocyte migration to lymphoid organs involves organ-specific homing receptors. The mouse peripheral lymph node homing receptor, defined by the MEL-14 monoclonal antibody (mAb), is a lectin-like cell surface protein, which is rapidly down-regulated upon cell activation with phorbol 12-myristate 13-acetate. We have raised mAbs against rapidly shed molecules released from the cell surface of activated human leukocytes. Five mAbs, DREG-55, -56, 110, -152, and -200, define an 80- to 85-kDa molecule involved in human lymphocyte recognition of peripheral lymph node (PLN) high endothelial venules (HEVs). The DREG-56 mAb specifically inhibits > 90% of binding of human lymphocytes to HEVs within frozen sections of peripheral but not mucosal lymphoid tissue. Furthermore, the gp80 antigen is expressed on lymphoid cell lines that are capable of binding to PLN HEVs. The DREG-56 mAb also inhibits lymphocyte binding of the phosphomannan monoester core from Hansenula hostii Y-2448, an activity associated with human and mouse lymphocyte recognition of PLN HEVs. Finally, all five DREG mAbs specifically stain COS cells transfected with LAM-1 cDNA, a putative human homologue of mouse MEL-14 antigen. These results demonstrate that the DREG mAbs define a human lymphocyte homing receptor for PLN HEVs and indicate that this human antigen is homologous to the MEL-14-defined murine lymphocyte homing receptor.