IDENTIFICATION OF CLQ AS THE HEAT-LABILE SERUM COFACTOR REQUIRED FOR IMMUNE-COMPLEXES TO STIMULATE ENDOTHELIAL EXPRESSION OF THE ADHESION MOLECULES E-SELECTIN AND INTERCELLULAR AND VASCULAR CELL-ADHESION MOLECULES-1
IDENTIFICATION OF CLQ AS THE HEAT-LABILE SERUM COFACTOR REQUIRED FOR IMMUNE-COMPLEXES TO STIMULATE ENDOTHELIAL EXPRESSION OF THE ADHESION MOLECULES E-SELECTIN AND INTERCELLULAR AND VASCULAR CELL-ADHESION MOLECULES-1
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DOI：
10.1073/pnas.92.18.8378
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发表时间：
1995-08-29
影响因子：
11.1
通讯作者：
CRONSTEIN, BN
中科院分区：
文献类型：
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作者：
LOZADA, C;LEVIN, RI;CRONSTEIN, BN
为了研究补体成分作为内皮细胞粘附分子表达调节剂在免疫复合物（IC）应答中的作用，我们确定了IC是否刺激内皮细胞对白细胞的粘附以及E-选择素和细胞间及血管细胞粘附分子1的表达。（ICAM-1和VCAM-1），我们发现，IC [牛血清白蛋白（BSA）-抗-BSA]刺激内皮细胞在补体充足的正常人血清（NHS）存在下增加白细胞但在热灭活血清（HIS）存在下或在单独的组织培养基中不能。去除血清中的补体成分C_3或C_8并不能阻止IC刺激的内皮细胞增殖，相反，去除补体成分C_1q可显著抑制IC刺激的内皮细胞增殖，当将热不稳定补体成分C_1q加入HIS中时，IC刺激内皮细胞增殖的能力完全恢复，Clq在介导IC对内皮细胞的作用中的可能作用的进一步证据是在内皮细胞表面上存在100-至126-kDa Clq结合蛋白的发现（通过细胞荧光照相术）和静息内皮细胞中33-kDa Clq受体的信息（通过逆转录-PCR），放线菌酮抑制蛋白质合成阻断了白细胞介素1或IC刺激的白细胞在NHS存在下的内皮细胞凋亡。在NHS存在下，用IC刺激后，内皮细胞表达的粘附分子数量增加，（E-选择素、ICAM-1和VCAM-1），粘附分子的内皮表达至少部分介导白细胞的内皮粘附，因为白细胞粘附被针对E-选择素的单克隆抗体阻断，这些研究表明，IC刺激内皮细胞表达粘附蛋白的白细胞在热不稳定血清因子的存在下，该因子似乎是C1q。
To examine the role of complement components as regulators of the expression of endothelial adhesive molecules in response to immune complexes (ICs), we determined whether ICs stimulate both endothelial adhesiveness for leukocytes and expression of E-selectin and intercellular and vascular cell adhesion molecules 1 (ICAM-1 and VCAM-1), We found that ICs [bovine serum albumin (BSA)-anti-BSA] stimulated endothelial cell adhesiveness for added leukocytes in the presence of complement-sufficient normal human serum (NHS) but not in the presence of heat-inactivated serum (HIS) or in tissue culture medium alone. Depletion of complement component C3 or C8 from serum did not prevent enhanced endothelial adhesiveness stimulated by ICs, In contrast, depletion of complement component Clq markedly inhibited IC-stimulated endothelial adhesiveness for leukocytes, When the heat-labile complement component Clq was added to HIS, the capacity of ICs to stimulate endothelial adhesiveness for leukocytes was completely restored, Further evidence for the possible role of Clq in mediating the effect of ICs on endothelial cells was the discovery of the presence of the 100- to 126-kDa Clq-binding protein on the surface of endothelial cells (by cytofluorography) and of message for the 33-kDa Clq receptor in resting endothelial cells (by reverse transcription-PCR), Inhibition of protein synthesis by cycloheximide blocked endothelial adhesiveness for leukocytes stimulated by either interleukin 1 or ICs in the presence of NHS. After stimulation with ICs in the presence of NHS, endothelial cells expressed increased numbers of adhesion molecules (E-selectin, ICAM-1, and VCAM-1), Endothelial expression of adhesion molecules mediated, at least in part, endothelial adhesiveness for leukocytes, since leukocyte adhesion was blocked by monoclonal antibodies directed against E-selectin, These studies show that ICs stimulate endothelial cells to express adhesive proteins for leukocytes in the presence of a heat-labile serum factor, That factor appears to be C1q.