Chang Rudy T, Fisher Mark J, Sumbria Rachita K
Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, Irvine, CA, USA.
Department of Neurology, University of California, Irvine, Irvine, CA, USA.
Fluids Barriers CNS. 2025 Apr 1;22(1):30. doi: 10.1186/s12987-025-00637-w.
Brain microvascular endothelial cells (BECs) lining the brain capillaries form the anatomical site of the blood-brain barrier (BBB), providing a highly selective barrier to support brain homeostasis and function. While the BBB acts as a barrier to immune cells and pathogens under normal conditions, BECs can facilitate their entry into the CNS via a phagocytosis-like mechanism. A similar process is now increasingly reported for a diverse set of cargos, resulting in the categorization of BECs as "non-professional" phagocytes and redefining the conventional view that these cells are functionally non-phagocytic. This review aims to summarize research demonstrating the capacity of BECs to phagocytose various cargos, including aged red blood cells (RBC), myelin debris, and embolic particles. Mechanistically, BEC phagocytosis can be triggered by the exposure of phosphatidylserine on RBC, expression of adhesion molecules such as ICAM-1 and VCAM-1 on BECs, cargo-opsonization, and/or involve BEC cytoskeleton remodeling. Phagocytic activity by BECs has significant clinical implications ranging from regulation of cerebral microvascular patency (particularly by contributing to and resolving capillary stalling), clearance of brain parenchymal debris, and brain parenchymal invasion by pathogens. Further, BEC phagocytosis of RBC, which represents a cell (RBC)-in-cell (BEC) phenomenon, is implicated in hemorrhagic lesions including cerebral microhemorrhages. This review aims to shed light on BEC phagocytosis as an important function within the brain microvascular system and will delve into the underlying mechanisms, discuss the clinical implications, and identify gaps in our understanding of this phenomenon.
脑毛细血管内衬的脑微血管内皮细胞（BECs）构成了血脑屏障（BBB）的解剖学部位，提供了一个高度选择性的屏障以维持脑内稳态和功能。虽然在正常情况下血脑屏障对免疫细胞和病原体起到屏障作用，但BECs可通过一种类似吞噬作用的机制促进它们进入中枢神经系统。现在越来越多地报道了针对多种不同货物的类似过程，这导致BECs被归类为“非专职”吞噬细胞，并重新定义了这些细胞在功能上是非吞噬性的传统观点。这篇综述旨在总结研究，证明BECs吞噬各种货物的能力，包括衰老的红细胞（RBC）、髓鞘碎片和栓塞颗粒。从机制上讲，BEC吞噬作用可由红细胞上磷脂酰丝氨酸的暴露、BECs上细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）等黏附分子的表达、货物调理作用和/或涉及BEC细胞骨架重塑来触发。BECs的吞噬活性具有重大的临床意义，范围从调节脑微血管通畅性（特别是通过促进和解决毛细血管停滞）、清除脑实质碎片以及病原体对脑实质的侵袭。此外，BECs对红细胞的吞噬作用，这是一种细胞（红细胞）在细胞（BEC）内的现象，与包括脑微出血在内的出血性病变有关。这篇综述旨在阐明BEC吞噬作用是脑微血管系统内的一项重要功能，并将深入探讨其潜在机制、讨论临床意义，并确定我们对这一现象理解上的差距。
