Departments of Medicine and Pathology, Stony Brook University , Stony Brook, NY , USA.
Departments of Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, and Laboratory Medicine and Pathology, Weill-Cornell Medical College , New York, NY , USA.
Front Immunol. 2014 Jun 26;5:278. doi: 10.3389/fimmu.2014.00278. eCollection 2014.
The ability of circulating blood monocytes to express C1q receptors (cC1qR and gC1qR) as well as to synthesize and secrete the classical pathway proteins C1q, C1r, and C1s and their regulator, C1-INH is very well established. What is intriguing, however, is that, in addition to secretion of the individual C1 proteins monocytes are also able to display macromolecular C1 on their surface in a manner that is stable and functional. The cell surface C1 complex is presumably formed by a Ca(2+)-dependent association of the C1r2⋅C1s2 tetramer to C1q, which in turn is anchored via a membrane-binding domain located in the N-terminus of its A-chain as shown previously. Monocytes, which circulate in the blood for 1-3 days before they move into tissues throughout the body, not only serve as precursors of macrophages and dendritic cells (DCs), but also fulfill three main functions in the immune system: phagocytosis, antigen presentation, and cytokine production. Since the globular heads of C1q within the membrane associated C1 are displayed outwardly, we hypothesize that their main function - especially in circulating monocytes - is to recognize and capture circulating immune complexes or pathogen-associated molecular patterns in the blood. This in turn may give crucial signal, which drives the monocytes to migrate into tissues, differentiate into macrophages or DCs, and initiate the process of antigen elimination. Unoccupied C1q on the other hand may serve to keep monocytes in a pre-dendritic phenotype by silencing key molecular players thus ensuring that unwarranted DC-driven immune response does not occur. In this paper, we will discuss the role of monocyte/DC-associated C1q receptors, macromolecular C1 as well as secreted C1q in both innate and acquired immune responses.
循环血液单核细胞表达 C1q 受体（cC1qR 和 gC1qR）以及合成和分泌经典途径蛋白 C1q、C1r 和 C1s 及其调节剂 C1-INH 的能力已得到充分证实。然而，有趣的是，除了分泌单个 C1 蛋白外，单核细胞还能够以稳定且功能的方式在其表面展示大分子 C1。细胞表面 C1 复合物推测是通过 C1r2⋅C1s2 四聚体与 C1q 之间的 Ca(2+)依赖性缔合形成的，如前所述，C1q 通过其 A 链 N 端的膜结合结构域锚定。单核细胞在进入全身组织之前在血液中循环 1-3 天，不仅作为巨噬细胞和树突状细胞 (DC) 的前体细胞，而且在免疫系统中发挥三种主要功能：吞噬作用、抗原呈递和细胞因子产生。由于膜结合 C1 中的 C1q 球状头部向外展示，我们假设它们的主要功能 - 特别是在循环单核细胞中 - 是识别和捕获血液中的循环免疫复合物或病原体相关分子模式。这反过来又可能提供关键信号，驱动单核细胞迁移到组织中，分化为巨噬细胞或 DC，并启动抗原消除过程。另一方面，未占据的 C1q 可能通过沉默关键分子参与者来使单核细胞保持在预先树突状表型，从而确保不会发生不必要的 DC 驱动的免疫反应。在本文中，我们将讨论单核细胞/DC 相关 C1q 受体、大分子 C1 以及分泌型 C1q 在固有和获得性免疫反应中的作用。
