Yamashiro S, Kamohara H, Wang J M, Yang D, Gong W H, Yoshimura T
Laboratory of Molecular Immunoregulation, National Cancer Institute at Frederick, Frederick, Maryland, USA.
J Leukoc Biol. 2001 May;69(5):698-704.
Polymorphonuclear leukocytes (PMN) are the most abundant leukocytes, comprising about two-thirds of peripheral blood leukocytes, and play major roles in innate immunity. In addition, PMN play critical roles in the development of adaptive immunity. Recently, defensins and other peptides pre-stored in PMN granules were shown to attract monocytes, dendritic cells, and T cells, leading to the hypothesis that the release of PMN granular peptides may link innate and adaptive immunity. During the past several years, we have focused on an alternative hypothesis that activated PMN further differentiate and acquire new phenotypes and functions that enable them to link the two responses. To test our hypothesis, we have taken local and global approaches and have shown several key findings that support the hypothesis. The findings include the requirement for priming PMN by cytokines to induce the delayed expression of MCP-1/CCL2, a signal for mononuclear cells, and the expression of new cell-surface markers by such cytokine-activated PMN. In the present manuscript, we focus on the phenotypic and functional changes that occur during PMN activation with selected cytokines. The results of our study indicate that inflammatory PMN are heterogeneous and play roles in not only innate but also adaptive immunity in response to stimuli released in injured tissues.
多形核白细胞(PMN)是最丰富的白细胞,约占外周血白细胞的三分之二,在固有免疫中起主要作用。此外,PMN在适应性免疫的发展中也起着关键作用。最近,PMN颗粒中预先储存的防御素和其他肽被证明可吸引单核细胞、树突状细胞和T细胞,从而提出了PMN颗粒肽的释放可能连接固有免疫和适应性免疫的假说。在过去几年中,我们专注于另一种假说,即活化的PMN会进一步分化并获得新的表型和功能,使其能够连接这两种反应。为了验证我们的假说,我们采用了局部和整体的方法,并展示了几个支持该假说的关键发现。这些发现包括细胞因子引发PMN以诱导单核细胞信号MCP-1/CCL2的延迟表达,以及此类细胞因子活化的PMN表达新的细胞表面标志物。在本手稿中,我们重点关注在PMN被选定细胞因子激活过程中发生的表型和功能变化。我们的研究结果表明,炎性PMN是异质性的,不仅在固有免疫中起作用,而且在对损伤组织中释放的刺激的适应性免疫中也起作用。