GLOBULAR DOMAIN LAMININ PEPTIDES STIMULATE NEUTROPHIL MOTILITY

在炎症反应过程中，中性粒细胞穿过基底 膜，并可能与丰富的基底糖蛋白，层粘连蛋白相互作用。 中性粒细胞含有多种蛋白水解酶，特别是 将层粘连蛋白A和B链降解成更小的片段。这项研究是 以确定完整的层粘连蛋白或10个合成肽 对应于层粘连蛋白A和B1链的不同区域刺激 人中性粒细胞趋化和激活的随机迁移(趋化运动)。 多肽F-9、F-11、F-12和F-13源自层粘连蛋白B1链 跨区，而层粘连蛋白A链衍生出六个肽： 来自氨基末端顶球的多肽Tg-1；多肽GD-1，GD-3， 来自羧基末端球状结构域的GD-6和GD-7；以及多肽AG-1 从上方的羧基末端的球状结构域。层粘连蛋白与多肽 在1-200微克/毫升的浓度范围内进行了评价 化验。只有F-12、TG-1、GD-6和GD-1四种多肽被刺激 中性粒细胞化学动力学迁移。层粘连蛋白和其他多肽未能 刺激人中性粒细胞迁移。相反，层粘连蛋白刺激兔 外周血中中性粒细胞趋化运动。这些结果证明了一个物种 人和兔中性粒细胞对层粘连蛋白运动反应的差异。三 来自层粘连蛋白A链的多肽、TG-1、GD-6和GD-1，以及一个肽 从B1链，F-12，刺激人PMN的化学运动迁移。这些 结果表明，完整的基底膜层粘连蛋白不直接 刺激人血中性粒细胞运动，然而，选择层粘连蛋白 基底膜过程中可能产生的多肽序列 降解可以刺激人中性粒细胞的运动。

During an inflammatory response, neutrophils move through the basement membrane and may interact with the abundant basement glycoprotein, laminin. Neutrophils contain a variety of proteolytic enzymes which specifically degrade the laminin A and B chains into smaller fragments. This study was undertaken to determine whether intact laminin or ten synthetic peptides corresponding to various regions of the laminin A and B1 chains stimulate human neutrophil chemotaxis and activated random migration (chemokinesis). Peptides F-9, F-11, F-12, and F-13 were derived from the laminin B1 chain cross-region, while six peptides were derived from the laminin A chain: 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 indicate that intact basement membrane laminin does not directly stimulate human blood neutrophil motility, however, selected laminin peptide sequences which may be generated during basement membrane degradation can stimulate human neutrophil motility.