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: 3792617
• 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/3792617
• 关键词: cell communication molecule; cell migration; chemoattractants; chemotaxis; human tissue; laminin; neutrophil; peptides; protein sequence; 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, 97:141): peptide TG-1 from the amino terminus top globule; peptides GD-1, 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. In contrast, laminin stimulated rabbit peripheral blood PMN chemokinesis. These results demonstrate a species difference in human and rabbit PMN motility responses to laminin. Three peptides from the laminin A chain, TG-1, GD-6, and GD-1, and one peptide from the B1 chain, F-12, stimulate human PMN chemokinetic migration. These results suggest that specific laminin fragments which may be generated during basement membrane degradation can stimulate human neutrophil migration. The results of this study were presented at the 1991 American Society for Cell Biology Meeting and are submitted for publication as a manuscript.

据报道，层粘连蛋白是一种 850 Kda 的基底膜糖蛋白 刺激兔腹膜渗出液的定向细胞迁移（趋化性） 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 的化学引诱活性仍不清楚。 层粘连蛋白，从 Engelbreth-Holm-Swarm 肿瘤中分离出来，以及十种合成的 对应于层粘连蛋白 A 和 B1 链各个区域的肽 比较了它们刺激人类中性粒细胞趋化性的能力， 通过聚碳酸酯膜激活随机迁移（趋化作用） 48 孔微趋化性测定中的过滤器。 肽 F-9、F-11、F-12 和 F-13 源自层粘连蛋白 B1 链交叉区 (J. Cell Biol. 1988, 107:1253)，而六种肽源自层粘连蛋白 A 链 (J. Invest. Derm., 1991, 97:141)：来自氨基末端顶部的肽 TG-1 小球;羧基末端的肽 GD-1、GD-3、GD-6 和 GD-7 球状结构域；和来自球状羧基末端上方的肽 AG-1 领域。 在一定浓度范围内评估层粘连蛋白和肽 在活力测定中为 1-200 ug/ml。 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中性粒细胞迁移。 相比之下， 层粘连蛋白刺激兔外周血PMN趋化作用。 这些结果 证明人和兔子 PMN 运动反应存在物种差异 层粘连蛋白。 来自层粘连蛋白 A 链的三种肽，TG-1、GD-6 和 GD-1， B1 链中的一种肽 F-12 可刺激人类 PMN 趋化动力学 迁移。 这些结果表明，特定的层粘连蛋白片段可能 基底膜降解过程中产生的能刺激人体 中性粒细胞迁移。 这项研究的结果发表在 1991 年美国学会上 细胞生物学会议并作为手稿提交出版。