LAMIN PEPTIDES STIMULATE HUMAN NEUTROPHIL CHEMOKINESIS

核纤层蛋白肽刺激人类中性粒细胞趋化作用

• 批准号: 3804886
• 负责人: L HARVATH
• 金额: --
• 依托单位: CENTER BIOLOGICS EVALUATION RESEARCH HEMATOLOGY
• 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/3804886
• 关键词: basement membrane; biological signal transduction; cell communication molecule; cell migration; chemoattractants; chemotaxis; glycoprotein structure; human tissue; laminin; leukocyte activation /transformation; neutrophil; receptor expression; ultrafiltration

Laminin, an 850 kDa basement membrane glycoprotein, has been reported to stimulate directed cell migration (chemotaxis) of rabbit peritoneal exudate neutrophils (PMN). Human PMN express receptors for laminin, however, the chemoattractant activity of laminin for human PMN remains undefined. Laminin, isolated from Engelbreth-Holm-Swarm tumor, and ten synthetic peptides corresponding to various regions of the laminin A and B1 chains were compared for their abilities to stimulate human PMN chemotaxis and activated random migration (chemokinesis) through polycarbonate membrane filters in a 48-well microchemotaxis assay. Peptides F-9, F-11, F-12, and F-13 were derived from the laminin B1 chain cross-region (J. Cell Biol. 1988, 107: 1253), while six peptides were derived from the laminin A chain (J. Invest. Derm., 1991, 97:14): peptide TG-1 from the amino terminus top globule; peptides GD1, GD-3, GD-6, and GD-7 from the carboxy terminus globular domain; and peptide AG-1 from above the carboxy terminus globular domain. Laminin and the peptides were evaluated over a concentration range of 1-200 ug/mL in the motility assays. Only four of the peptides, F-12, TG-1, GD-6 and Gd-1, stimulated PMN chemokinetic migration. Laminin and the other peptides failed to stimulate human PMN migration. These results demonstrate that intact laminin does not stimulate human PMN migration. Three peptides from the laminin A chain, TG-1, GD-6 and GD-1, and one peptide from the B1 chain, F-12, stimulate chemokinetic migration. These results suggest that specific laminin fragments which may be generated during degradation of the basement membrane can stimulate human neutrophil migration. The results of this study have been submitted for presentation at the 1991 American Society for Cell Biology Meeting.

据报道，层粘连蛋白是一种 850 kDa 的基底膜糖蛋白 刺激兔腹膜的定向细胞迁移（趋化性） 渗出中性粒细胞（PMN）。 人类 PMN 表达层粘连蛋白受体， 然而，层粘连蛋白对人类 PMN 的趋化活性仍然存在 不明确的。 层粘连蛋白，从 Engelbreth-Holm-Swarm 肿瘤中分离出来，以及 10 对应于层粘连蛋白A的各个区域的合成肽和 比较 B1 链刺激人类 PMN 的能力 趋化性和激活的随机迁移（趋化作用） 48 孔微趋化性测定中的聚碳酸酯膜过滤器。 肽 F-9、F-11、F-12 和 F-13 源自层粘连蛋白 B1 链跨区 (J. Cell Biol. 1988, 107: 1253)，而六种肽 衍生自层粘连蛋白 A 链 (J. Invest. Derm., 1991, 97:14)： 来自氨基末端顶部小球的肽 TG-1；肽 GD1、GD-3、 来自羧基末端球状结构域的GD-6和GD-7；和肽 AG-1 来自羧基末端球状结构域上方。 层粘连蛋白和 在 1-200 ug/mL 的浓度范围内对肽进行评估 运动性测定。 只有四种肽：F-12、TG-1、GD-6 和 Gd-1， 刺激 PMN 趋化迁移。 层粘连蛋白和其他肽 未能刺激人类 PMN 迁移。 这些结果表明 完整的层粘连蛋白不会刺激人类中性粒细胞迁移。 三胜肽 来自层粘连蛋白 A 链、TG-1、GD-6 和 GD-1，以及来自 B1 链、F-12 刺激趋化迁移。 这些结果表明 特定的层粘连蛋白片段可能在 基底膜的降解可以刺激人类中性粒细胞 迁移。 该研究结果已提交至 1991 年美国细胞生物学学会会议。