Teixeira Jose Eduardo, Heron Bradley Thomas, Huston Christopher Dwight
Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA.
J Infect Dis. 2008 Oct 1;198(7):1062-70. doi: 10.1086/591628.
Entamoeba histolytica, the cause of invasive amebiasis, phagocytoses apoptotic host cells during tissue invasion. In mammals, collectin family members (e.g., mannose-binding lectin [MBL]) and the structurally related protein C1q bind to apoptotic cells and stimulate macrophage phagocytosis via a conserved collagenous tail domain. The collectins also bind to bacteria, the usual source of nutrients for E. histolytica.
To test the possibility that the collectins are ligands that stimulate E. histolytica phagocytosis, we used a flow cytometry-based assay for amebic phagocytosis, a method for making single-ligand particles to delineate a given ligand's ability to initiate phagocytosis, and purified human C1q, MBL, and collagenous collectin tails.
Apoptotic lymphocytes opsonized with serum or human C1q were phagocytosed more efficiently than control cells, an effect that was dependent on ligand density. C1q and the collectins alone were adequate to trigger amebic phagocytosis, because single-ligand particles coated with C1q, MBL, or purified collectin tails were phagocytosed more efficiently than control particles. Furthermore, C1q, MBL, and the tail domain of C1q were all chemoattractants for E. histolytica.
C1q and MBL can serve as opsonins on apoptotic cells that stimulate E. histolytica phagocytosis, an effect mediated at least in part by the collagenous collectin tail domain.
溶组织内阿米巴是侵袭性阿米巴病的病原体,在组织侵袭过程中吞噬凋亡的宿主细胞。在哺乳动物中,凝集素家族成员(如甘露糖结合凝集素[MBL])和结构相关蛋白C1q可结合凋亡细胞,并通过保守的胶原尾域刺激巨噬细胞吞噬作用。凝集素还可结合细菌,而细菌是溶组织内阿米巴通常的营养来源。
为了测试凝集素是否为刺激溶组织内阿米巴吞噬作用的配体,我们使用了基于流式细胞术的阿米巴吞噬测定法、制备单配体颗粒以描述给定配体引发吞噬作用能力的方法,以及纯化的人C1q、MBL和胶原凝集素尾。
用血清或人C1q调理的凋亡淋巴细胞比对照细胞更有效地被吞噬,这种效应取决于配体密度。单独的C1q和凝集素足以触发阿米巴吞噬作用,因为包被有C1q、MBL或纯化凝集素尾的单配体颗粒比对照颗粒更有效地被吞噬。此外,C1q、MBL和C1q的尾域对溶组织内阿米巴均为趋化剂。
C1q和MBL可作为凋亡细胞上的调理素,刺激溶组织内阿米巴吞噬作用,这种效应至少部分由胶原凝集素尾域介导。