Department of Medical Neurobiology, IMRIC, Hebrew University Hadassah Medical School and the Eric Roland Center for Neurodegenerative Diseases, Jerusalem, Israel.
Glia. 2010 May;58(7):823-30. doi: 10.1002/glia.20966.
Central nervous system (CNS) microglia (MG) and peripheral tissue macrophages (MO) remove pathogens by phagocytosis. Zymosan, a model yeast pathogen, is a beta-glucan rich particle that readily activates the complement system and then becomes C3bi-opsonized (op). Complement receptor-3 (CR3) has initially been implicated in mediating the phagocytosis of both C3bi-op and non-opsonized (nop) zymosan by MO through C3bi and beta-glucan binding sites, respectively. Later, the role of CR3 as a phagocytic beta-glucan receptor has been questioned and the supremacy of beta-glucan receptor Dectin-1 advocated. We compare here between primary mouse CNS MG and peripheral tissue MO with respect to CR3 and Dectin-1 mediated phagocytosis of C3bi-op and nop zymosan. We report that MG and MO display similar as well as dissimilar functional properties in this respect. Although CR3 and Dectin-1 function both as beta-glucan/non-opsonic receptors in MG during nop zymosan phagocytosis, Dectin-1, but not CR3, does so in MO. CR3 functions also as a C3bi/opsonic receptor in MG and MO during C3bi-op zymosan phagocytosis, leading to phagocytosis which is more efficient than that of nop zymosan. Dectin-1 contributes, albeit less than CR3, to phagocytosis of C3bi-op zymosan in MG and further less in MO, suggesting that C3bi-opsonization does not block all beta-glucan sites on zymosan from binding Dectin-1 on phagocytes. Thus, altogether CR3 and Dectin-1 contribute both to phagocytosis of nop and C3bi-op zymosan in MG, whereas MO switch from CR3-independent/Dectin-1-dependent phagocytosis of nop zymosan to phagocytosis of C3bi-op zymosan where CR3 dominates over Dectin-1.
中枢神经系统 (CNS) 小胶质细胞 (MG) 和外周组织巨噬细胞 (MO) 通过吞噬作用清除病原体。酵母病原体酵母聚糖是一种富含β-葡聚糖的颗粒，很容易激活补体系统，然后被 C3bi 调理 (op)。补体受体 3 (CR3) 最初被认为通过 C3bi 和β-葡聚糖结合位点分别介导 MO 对 C3bi-op 和非调理 (nop) 酵母聚糖的吞噬作用。后来，CR3 作为吞噬β-葡聚糖受体的作用受到质疑，而 Dectin-1 作为 β-葡聚糖受体的优势得到了提倡。我们在这里比较了初级小鼠 CNS MG 和外周组织 MO 对 C3bi-op 和 nop 酵母聚糖的 CR3 和 Dectin-1 介导的吞噬作用。我们报告说，MG 和 MO 在这方面表现出相似和不同的功能特性。虽然在 nop 酵母聚糖吞噬过程中，CR3 和 Dectin-1 在 MG 中均作为β-葡聚糖/非调理受体发挥作用，但在 MO 中仅 Dectin-1 发挥作用。在 MG 和 MO 中，CR3 还作为 C3bi-op 的调理受体发挥作用，导致吞噬作用比 nop 酵母聚糖更有效。Dectin-1 虽然不如 CR3 那样有助于 C3bi-op 酵母聚糖的吞噬，但在 MG 中的贡献较小，在 MO 中的贡献更小，这表明 C3bi 调理不会阻止所有与调理酵母聚糖结合的β-葡聚糖位点与吞噬细胞上的 Dectin-1 结合。因此，总的来说，CR3 和 Dectin-1 都有助于 MG 中 nop 和 C3bi-op 酵母聚糖的吞噬作用，而 MO 则从依赖于 CR3 和依赖于 Dectin-1 的 nop 酵母聚糖吞噬作用转变为依赖于 CR3 且 Dectin-1 优势的 C3bi-op 酵母聚糖吞噬作用。
