Endothelial cells and macrophages as allies in the healthy and diseased brain

Abstract

Diseases of the central nervous system (CNS) are often associated with vascular disturbances or inflammation and frequently both. Consequently, endothelial cells and macrophages are key cellular players that mediate pathology in many CNS diseases. Macrophages in the brain consist of the CNS-associated macrophages (CAMs) [also referred to as border-associated macrophages (BAMs)] and microglia, both of which are close neighbours or even form direct contacts with endothelial cells in microvessels. Recent progress has revealed that different macrophage populations in the CNS and a subset of brain endothelial cells are derived from the same erythromyeloid progenitor cells. Macrophages and endothelial cells share several common features in their life cycle—from invasion into the CNS early during embryonic development and proliferation in the CNS, to their demise. In adults, microglia and CAMs have been implicated in regulating the patency and diameter of vessels, blood flow, the tightness of the blood–brain barrier, the removal of vascular calcification, and the life-time of brain endothelial cells. Conversely, CNS endothelial cells may affect the polarization and activation state of myeloid populations. The molecular mechanisms governing the pas de deux of brain macrophages and endothelial cells are beginning to be deciphered and will be reviewed here.

CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology

“…Moreover, the same study showed that neutrophils preferentially extravasate into the circumscribed locations adjacent to PVMs. In our case, PVMs are in an ideal anatomical position to contribute to focal chemokine gradients [ 8 , 9 ], which may either be transported to the luminal surface of endothelial cells and/or act as a migratory signal for peripheral immune cells. Data from isolated CAMs in naïve conditions revealed their ability to produce different chemoattractants under physiological conditions, including different interleukins and chemokines [ 18 ] involved in neutrophil recruitment [ 14 , 30 , 32 , 34 , 35 , 41 ].…”

“…CAMs are a distinct population of brain resident macrophages located within CNS interfaces, which include the perivascular spaces (perivascular macrophages, PVMs), the leptomeninges (meningeal macrophages, MMs), and the choroid plexus (choroid plexus macrophages, ChPM) and are identified in human and mouse brain as CD163 + and CD206 + cells, respectively [ 12 ]. Recent studies have indicated that CAMs are involved in a wide variety of pathological states [ 8 , 9 , 23 , 48 ]. Their main functions, as described to date, include regulation of blood–brain barrier (BBB) integrity and cerebrospinal fluid (CSF) dynamics, phagocytosis of blood-borne pathogens, and control of leukocyte migration [ 10 , 27 ].…”

Responses of Endothelial Progenitor Cells to Chronic and Acute Physical Activity in Healthy Individuals

“…This specific relation may be attributed to direct cell-to-cell contact, secretion of cytokines, chemokines, growth factors, or exosomal vesicles. It is known that EPCs’ relation with macrophages in the brain plays a critical role in regulating blood–brain barrier function, vascular perfusion, and inflammation [ 105 ]. Similar close relations exist in the maintenance of muscular biology/regeneration and bone homeostasis [ 106 , 107 , 108 ].…”