LAMININ RECEPTOR IN LEUKOCYTES

白细胞中的层粘连蛋白受体

• 批准号: 4691717
• 负责人: G J BRYANT
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4691717
• 关键词: cell adhesion; cell growth regulation; cell migration; chemotaxis; extracellular matrix; metastasis; monoclonal antibody; neoplasm /cancer invasiveness; neoplastic cell; neutrophil; peptides; radiotracer

Previous studies on the mechanism of leukocyte traversal of basement membranes showed that rabbit peritoneal exudate cells (PMN) preferentially used laminin, a major constituent of basement membrane, to attach to another component, type IV collagen. PMN also responded chemotactically to nanomolar levels of laminin. We have now determined that PMN possess a receptor for laminin. Scatchard analysis using I125-laminin indicate a single class of saturable high affinity binding sites (kd = 6.15 nM/L) on PMN and 3.6 x 10,000 sites per cell. A chymotryptically derived fragment of laminin, C1 which retains the cell binding site gave similar results. Immunoperoxidase studies using monoclonal antibodies to the laminin receptor indicated the presence of the receptor on PMN cell surfaces. PMN responded chemotactically to nanomolar levels of C1 and laminin, a result consonant with binding data. PMN chemotaxis to a formyl peptide was markedly inhibited by the monoclonal antibodies, suggesting that the laminin receptor may be required for PMN chemotaxis in general. Our results suggest that PMN extravasation across basement membranes is aided both by reversible attachment of the cells to laminin in the matrix and by chemotaxis to a gradient of soluble intact and possibly degraded laminin. These characteristics have much in common with those of highly metastatic tumor cells.

白细胞穿越基底膜机制的研究进展 结果表明，兔腹腔渗出液细胞（PMN） 使用层粘连蛋白，一种基底膜的主要成分， 另一种成分IV型胶原蛋白。 中性粒细胞也对 纳摩尔水平的层粘连蛋白。 我们现在已经确定PMN拥有 层粘连蛋白受体。 使用I125-层粘连蛋白的Scatchard分析表明， 单一类别的可饱和高亲和力结合位点（kd = 6.15 nM/L） PMN和3.6 x 10，000个站点/小区。 胰凝乳蛋白酶衍生的片段 层粘连蛋白，保留细胞结合位点的C1得到类似的结果。 层粘连蛋白单克隆抗体免疫过氧化物酶研究 受体的表达表明PMN细胞表面存在该受体。 PMN 对纳摩尔水平的C1和层粘连蛋白产生化学反应， 与绑定数据一致。 中性粒细胞对甲酰基肽的趋化性为 单克隆抗体明显抑制，表明 层粘连蛋白受体通常可能是PMN趋化性所必需的。 我们 结果表明，有助于中性粒细胞渗出基底膜 通过细胞与基质中的层粘连蛋白的可逆附着， 对可溶性完整和可能降解的层粘连蛋白的梯度的趋化性。 这些特征与高转移性乳腺癌有许多共同之处。 肿瘤细胞