From blood to brain: amoeboid microglial cell, a nascent macrophage and its functions in developing brain

Abstract

Amoeboid microglial cells (AMC) in the developing brain are active macrophages. The macrophagic nature of these cells has been demonstrated by many methods, such as the localization of various hydrolytic enzymes and the presence of complement type 3 surface receptors in them. More importantly is the direct visualization of these cells engaged in the phagocytosis of degenerating cells at the ultrastructural level. Further evidence of them being active macrophages is the avid internalization of tracers administered by the intravenous or intraperitoneal routes in developing rats. The potential involvement of AMC in immune functions is supported by the induced expression of major histocompatibility complex class I and II antigens on them when challenged by lipopolysaccharide or interferon-γ. Immunosuppressive drugs, such as glucocorticoids and immune function-enhancing drugs like melatonin, affect the expression of surface receptors and antigens and the release of cytokines by AMC. Recent studies in our laboratory have shown the expression of insulin-like growth factors, endothelins, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and N-methyl-D-asparate receptors. This along with the release of chemokines, such as stromal derived factor-1a and monocyte chemoattractant protein-1, suggests multiple functional roles of AMC in early brain development.

The 18-kDa Mitochondrial Translocator Protein in Human Gliomas: An 11C-(R)PK11195 PET Imaging and Neuropathology Study

“…We also demonstrated that TSPO was detectable only in a subpopulation of microglia and macrophages, overall accounting for about 16% of GAMs. This observation overcomes the general assumption from studies on neurodegenerative and neuroinflammatory conditions that almost all activated microglial cells are TSPO-positive and therefore that a high proportion of 11 C-(R)PK11195 binding relates to microglial TSPO (34,35). The reason for TSPO downregulation in GAMs is unclear.…”

Hypertonic saline attenuates expression of Notch signaling and proinflammatory mediators in activated microglia in experimentally induced cerebral ischemia and hypoxic BV-2 microglia

“…iNOS and ROS are known to be involved in oxidative stress that was indicated to contribute to the death of neurons and glia [48, 49]. Activated microglial cells are thought to be the main origin of inflammatory mediators and crucially involved in neuronal damage in the penumbra in ischemia stroke [5–7]. Our previous study had shown that HS could suppress the release of inflammatory mediators, namely, TNF-α and IL-1β in activated microglia [26].…”

“…Increasing evidence has shown that neuroinflammatory mediators, which exert deleterious effects and exacerbate the progression of tissue damage, play crucial roles in the pathophysiology of cerebral ischemia injury [3, 4]. A variety of inflammatory mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), nitric oxide (NO), reactive oxygen species (ROS) are widely thought to be derived from activated microglia, which is the main resident immune cells within the central nervous system (CNS) that play an important role in the development of inflammatory response after cerebral ischemic insults [5–7]. Therefore, it seems to be a progressing therapeutic strategy to suppress the excessive inflammatory mediators driven by activated-microglia in cerebral ischemia.…”

Life and Death of Microglia

“…Microglial precursors can invade via the leptomeninges, from the ventricular zone, or by way of the vasculature, although with regard to the latter one should point out that macrophage infiltration of the neuroepithelium begins before vascular channels have even formed (Sorokin et al 1992), thus challenging the long-held view that bloodborne monocytes primarily give rise to microglial cells (Chan et al 2007;Streit 2001). Fetal macrophages persist through the perinatal period and until the second postnatal week in rodents at which time they are more commonly referred to as ameboid microglial cells (Kaur et al 2007;Ling and Wong 1993). They are highly proliferative, highly mobile, and phagocytic cells that are non-process-bearing with a rounded morphology which has prompted their designation as ameboid (Alliot et al 1991;Brockhaus et al 1996;Giulian and Ingeman 1988;Takahashi et al 1989).…”