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At least 199 records · Page 11Linked to original sources

PubMed2005

Vesicle-mediated transport and release of CCL21 in endangered neurons: a possible explanation for microglia activation remote from a primary lesion.

Whenever neurons in the CNS are injured, microglia become activated. In addition to local activation, microglia remote from the primary lesion site are stimulated. Because this so-called secondary activation of microglia is instrumental for long-term changes after neuronal injury, it is important to understand how microglia activity is controlled. The remote activation of microglia implies that the activating signals are transported along neuronal projections. However, the identity of these signals has not yet been identified. It is shown here that glutamate-treated neurons rapidly express and release the chemokine CCL21. We also provide evidence that neuronal CCL21 is packed in vesicles and transported throughout neuronal processes to reach presynaptic structures. Chemotaxis assays show that functional CCL21 is released from endangered neurons and activate microglia via the chemokine receptor CXCR3. Based on these findings, we suggest that neuronal CCL21 is important in directed neuron-microglia signaling and that this communication could account for the remote activation of microglia, far distant from a primary lesion.

Animals↗

PubMed2007

The Ca2+-activated K+ channel KCNN4/KCa3.1 contributes to microglia activation and nitric oxide-dependent neurodegeneration.

Brain damage and disease involve activation of microglia and production of potentially neurotoxic molecules, but there are no treatments that effectively target their harmful properties. We present evidence that the small-conductance Ca2+/calmodulin-activated K+ channel KCNN4/ KCa3.1/SK4/IK1 is highly expressed in rat microglia and is a potential therapeutic target for acute brain damage. Using a Transwell cell-culture system that allows separate treatment of the microglia or neurons, we show that activated microglia killed neurons, and this was markedly reduced by treating only the microglia with a selective inhibitor of KCa3.1 channels, triarylmethane-34 (TRAM-34). To assess the role of KCa3.1 channels in microglia activation and key signaling pathways involved, we exploited several fluorescence plate-reader-based assays. KCa3.1 channels contributed to microglia activation, inducible nitric oxide synthase upregulation, production of nitric oxide and peroxynitrite, and to consequent neurotoxicity, protein tyrosine nitration, and caspase 3 activation in the target neurons. Microglia activation involved the signaling pathways p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB), which are important for upregulation of numerous proinflammatory molecules, and the KCa3.1 channels were functionally linked to activation of p38 MAPK but not NF-kappaB. These in vitro findings translated into in vivo neuroprotection, because we found that degeneration of retinal ganglion cells after optic nerve transection was reduced by intraocular injection of TRAM-34. This study provides evidence that KCa3.1 channels constitute a therapeutic target in the CNS and that inhibiting this K+ channel might benefit acute and chronic neurodegenerative disorders that are caused by or exacerbated by inflammation.

Animals↗

PubMed2004

Microglia: neuroprotective and neurotrophic cells in the central nervous system.

Microglia are currently accepted as sensor cells in the central nervous system that respond to injury and brain disease. The main function of microglia is believed to be brain defense, as they are known to scavenge invading microorganisms and dead cells, and also to act as immune or immunoeffector cells. However, microglia are also thought to contribute to the onset of or to exacerbate neuronal degeneration and/or inflammation in many brain diseases by producing deleterious factors including superoxide anions, nitric oxide and inflammatory cytokines. Nonetheless, microglia have also been shown to act neuroprotectively by eliminating excess excitotoxins in the extracellular space. Moreover, there is accumulating evidence that microglia produce neurotrophic and/or neuroprotective molecules; in particular, it has been suggested that they promote neuronal survival in cases of brain injury. In general, the question of whether microglia act as neurotoxic cells or as neuroprotective cells in vivo has gained much recent attention. In this paper, we provide a review of findings indicating that the microglia are basically neurotrophic/neuroprotective cells in the nervous system. In addition, the mechanism by which neurotrophic microglia become oriented to a neurotoxic state is discussed.

Animals↗

PubMed2004

Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs.

Microglia are the resident macrophage-like population in the CNS. Microglia remain quiescent until injury or infection activates the cells to perform effector inflammatory and APC functions. Our previous studies have shown that microglia infected with a neurotropic strain of Theiler's murine encephalomyelitis virus secreted innate immune cytokines and up-regulated costimulatory molecules and MHC class II, enabling the cells to present viral and myelin Ags to CD4+ T cells. Recently, TLRs have been shown to recognize pathogen-associated molecular patterns and initiate innate immune responses upon interaction with infectious agents. We examined TLR expression on brain microglia and their functional responses upon stimulation with various TLR agonists. We report that mouse microglia express mRNA for all of the recently identified TLRs, TLR1-9, used for recognition of bacterial and viral molecular patterns. Furthermore, stimulation of quiescent microglia with various TLR agonists, including LPS (TLR4), peptidoglycan (TLR2), polyinosinic-polycytidylic acid (TLR3), CpG DNA (TLR9), and infection with viable Theiler's murine encephalomyelitis virus, activated the cells to up-regulate unique patterns of innate and effector immune cytokines and chemokines at the mRNA and protein levels. In addition, TLR stimulation activated up-regulation of MHC class II and costimulatory molecules, enabling the microglia to efficiently present myelin Ags to CD4+ T cells. Thus, microglia appear to be a unique and important component of both the innate and adaptive immune response, providing the CNS with a means to rapidly and efficiently respond to a wide variety of pathogens.

Animals↗

PubMed2006

Microglia proliferation is regulated by hydrogen peroxide from NADPH oxidase.

Microglia are resident brain macrophages that become activated and proliferate following brain damage or stimulation by immune mediators, such as IL-1beta or TNF-alpha. We investigated the mechanisms by which microglial proliferation is regulated in primary cultures of rat glia. We found that basal proliferation of microglia was stimulated by proinflammatory cytokines IL-1beta or TNF-alpha, and this proliferation was completely inhibited by catalase, implicating hydrogen peroxide as a mediator of proliferation. In addition, inhibitors of NADPH oxidase (diphenylene iodonium or apocynin) also prevented microglia proliferation, suggesting that this may be the source of hydrogen peroxide. IL-1beta and TNF-alpha rapidly stimulated the rate of hydrogen peroxide produced by isolated microglia, and this was inhibited by diphenylene iodonium, implying that the cytokines were acting directly on microglia to stimulate the NADPH oxidase. Low concentrations of PMA or arachidonic acid (known activators of NADPH oxidase) or xanthine/xanthine oxidase or glucose oxidase (generating hydrogen peroxide) also increased microglia proliferation and this was blocked by catalase, showing that NADPH oxidase activation or hydrogen peroxide was sufficient to stimulate microglia proliferation. In contrast to microglia, the proliferation of astrocytes was unaffected by the presence of catalase. In conclusion, these findings indicate that microglial proliferation in response to IL-1beta or TNF-alpha is mediated by hydrogen peroxide from NADPH oxidase.

Animals↗

PubMed2006

Microglia recognize double-stranded RNA via TLR3.

Microglia are CNS resident innate immune cells of myeloid origin that become activated and produce innate proinflammatory molecules upon encountering bacteria or viruses. TLRs are a phylogenetically conserved diverse family of sensors for pathogen-associated molecular patterns that drive innate immune responses. We have recently shown that mice deficient in TLR3 (TLR3(-/-) mice) are resistant to lethal encephalitis and have reduced microglial activation after infection with West Nile virus, a retrovirus that produces dsRNA. We wished to determine whether microglia recognize dsRNA through the TLR3 pathway. In vitro, murine wild-type primary cultured microglia responded to synthetic dsRNA polyinosinic-polycytidylic acid (poly(I:C)) by increasing TLR3 and IFN-beta mRNA and by morphologic activation. Furthermore, wild-type microglia dose dependently secreted TNF-alpha and IL-6 after poly(I:C) challenge, whereas TLR3(-/-) microglia produced diminished cytokines. Activation of MAPK occurred in a time-dependent fashion following poly(I:C) treatment of wild-type microglia, but happened with delayed kinetics in TLR3(-/-) microglia. As an in vivo model of encephalitis, wild-type or TLR3(-/-) mice were injected intracerebroventricularly with poly(I:C) or LPS, and microglial activation was assessed by cell surface marker or phospho-MAPK immunofluorescence. After intracerebroventricular injection of poly(I:C), microgliosis was clearly evident in wild-type mice but was nearly absent in TLR3(-/-) animals. When taken together, our results demonstrate that microglia recognize dsRNA through TLR3 and associated signaling molecules and suggest that these cells are key sensors of dsRNA-producing viruses that may invade the CNS.

Animals↗

PubMed1999

A Kv1.5 to Kv1.3 switch in endogenous hippocampal microglia and a role in proliferation.

The proliferation of microglia is a normal process in CNS development and in the defense against pathological insults, although, paradoxically, it contributes to several brain diseases. We have examined the types of voltage-activated K(+) currents (Kv) and their roles in microglial proliferation. Microglia were tissue-printed directly from the hippocampal region using brain slices from 5- to 14-d-old rats. Immediately after tissue prints were prepared, unipolar and bipolar microglia expressed a large Kv current, and the cells were not proliferating. Surprisingly, this current was biophysically and pharmacologically distinct from Kv1.3, which has been found in dissociated, cultured microglia, but it was very similar to Kv1.5. After several days in culture the microglia became highly proliferative, and although the Kv prevalence and current density decreased, many cells exhibited a prominent Kv that was indistinguishable from Kv1.3. The Kv1.5-like current was present in nonproliferating cells, whereas proliferating cells expressed the Kv1.3-like current. Immunocytochemical staining showed a dramatic shift in expression and localization of Kv1.3 and Kv1.5 proteins in microglia: Kv1.5 moving away from the surface and Kv1.3 moving to the surface as the cells were cultured. K(+) channel blockers inhibited proliferation, and the pharmacology of this inhibition correlated with the type of Kv current expressed. Our study, which introduces a method for the physiological examination of microglia from identified brain regions, demonstrates the differential expression of two functional Kv subunits and shows that a functional delayed rectifier current is necessary for microglia proliferation.

Animals↗

PubMed2001

Light-induced migration of retinal microglia into the subretinal space.

PURPOSE: To explore the effects of light exposure and deprivation on the distribution and function of microglia in the subretinal space of mice. METHODS: Using a monoclonal antibody, 5D4, that identifies resting, ramified microglia, the distribution and density of microglia in the retina, and the subretinal space were determined by confocal microscopy and by immunohistochemistry of cryopreserved sections of eyes of albino and pigmented mice exposed to diverse levels of light, ranging from complete darkness to intense brightness. Axotomized retinal ganglion cells were retrograde labeled by fluorescent tracer to determine whether the marker colocalizes to 5D4+ cells. Electron microscopy was used to evaluate microglia for evidence of phagocytosis. RESULTS: 5D4+ microglia in pigmented eyes were limited to the inner retinal layers, but in albino eyes 5D4+ cells were found in the outer retinal layers and subretinal space as well. The subretinal space of eyes of albino mice raised from birth in complete darkness contained few 5D4+ cells, but exposure to light caused the rapid accumulation of 5D4+ cells at this site. 5D4+ cell density in the subretinal space correlated directly with intensity of ambient light. Retrograde labeling of axotomized ganglion cells resulted in 5D4+ cells in the subretinal space that contained the retrograde label. Subretinal microglia contained phagocytized rod outer segment discs. On intense light exposure, 5D4+ cells adopted an active morphology, but failed to express class II major histocompatibility complex (MHC) molecules. CONCLUSIONS: Light exposure induced retinal microglia migration into the subretinal space in albino mice. Subretinal microglia appeared to augment through phagocytosis the capacity of pigment epithelium to take up the photoreceptor debris of light toxicity. The unexpected presence of these cells in the subretinal space raises questions concerning their potential contribution to immune privilege in this space and to the fate of retinal transplants.

Albinism↗

PubMed1996

Predominant expression of platelet-activating factor receptor in the rat brain microglia.

Cellular localization of platelet-activating factor (PAF) receptor in the rat brain was determined by (1) in situ hybridization, (2) Northern blot analysis in primary cell cultures of neurons, microglia, astrocytes, and fibroblasts, and (3) Ca2+ imaging in hippocampal culture. In situ hybridization revealed that the PAF receptor mRNA is expressed intensely in microglia and moderately in neurons. Northern blot analysis revealed that PAF receptor mRNA is the most abundant in microglia. In primary hippocampal cultures, PAF elevated intracellular Ca2+ concentration in microglia and also in neurons, but to a lesser extent. These results suggest predominant presence of PAF receptor in microglia. Cultured microglia also expressed cPLA2 mRNA the most intensely. PAF-activated microglia released arachidonic acid in a Ca(2+)-dependent manner and without conversion to its derivatives. We propose that microglia as well as neurons contribute to PAF-related events in the CNS by releasing arachidonic acid.

Animals↗

PubMed1998

Microglia are more efficient than astrocytes in antigen processing and in Th1 but not Th2 cell activation.

Microglia and astrocytes, two glial cell populations of the central nervous system, present Ag and stimulate T cell proliferation, but it is unclear whether they preferentially activate Th1 or Th2 responses. We have investigated the efficiency of microglia and astrocytes in the presentation of OVA peptide 323-339 or native OVA to Th1 and Th2 cell lines from DO11.10 TCR transgenic mice. Upon stimulation with IFN-gamma, microglia express MHC class II molecules, CD40, and ICAM-1 and efficiently present OVA 323-339, leading to T cell proliferation and production of IL-2 and IFN-gamma by Th1 and of IL-4 by Th2 cells. IFN-gamma-treated astrocytes, which express MHC class II and ICAM-1, present OVA 323-339 less efficiently to Th1 cells but are as efficient as microglia in inducing IL-4 secretion by Th2 cells. However, astrocytes are much less potent than microglia in presenting naturally processed OVA peptide to either T cell subset, indicating inefficient Ag processing. The capacity of astrocytes and microglia to stimulate Th1 and Th2 cells depends on their MHC class II expression and does not involve ICAM-1, B7-1, or B7-2 molecules. However, CD40-CD40L interactions contribute to Th1 activation by microglia. These data suggest that microglia may play a role in the activation of Th1 and Th2 cells, whereas astrocytes would restimulate mainly Th2 responses in the presence of appropriate peptides. This differential capacity of brain APC to restimulate Th1 and Th2 responses may contribute to the reactivation and regulation of local inflammatory processes during infectious and autoimmune diseases.

Animals↗

PubMed1991

Diversity amongst the microglia in growing and regenerating fish CNS: immunohistochemical characterization using FL.1, an anti-macrophage monoclonal antibody.

We have immunohistochemically characterized the forms and distribution of microglia--the macrophages of the CNS--in fish, using a new monoclonal antibody (mAb), FL.1. This mAb specifically reacts with resident macrophages throughout the body in Oreochromine fish, including Kuppfer cells, gut-associated myeloid cells, and peritoneal macrophages, as well as with microglia, but circulating monocytes are not labelled with FL.1. The FL.1-epitope, which is lost following treatment with reducing agents, has an extracellular location and is associated with three integral membrane glycoprotein variants. FL.1-staining shows that microglia are extremely abundant throughout the fish CNS. For example, they comprise a third of the glia in the optic nerve, and 30% of all cells, including neurons, in the spinal cord, i.e., fish have about tenfold more microglia than mammals. Two forms of FL.1-positive microglia are predominant in fish, one resembling their mammalian counterparts, but less ramified, and the other comprising smaller rounded cells with very little cytoplasm, which are most numerous in the ependymal region of the optic tectum. Apart from the conventional microglia, the optic nerves also contain large lipid-laden macrophages which comprise a third form of FL.1-positive cell in the CNS. Fish optic nerves contain astrocytes of a distinct type which form reticular networks, but lack connections to capillaries (Maggs and Scholes, J. Neurosci. 1990;10:1600-1614). The co-distribution of foamy macrophages may have a metabolic role that is performed by ordinary astrocytes elsewhere in the CNS. An antiserum against the beta 2 subunit of the human leukocyte integrins (Kishimoto et al., Cell 1987a; 50:193-202) was found selectively to recognize the foamy macrophages in Oreochromis. Following lesion to the optic nerve, FL.1-labelling shows that microglia proliferate throughout the visual pathway. In the optic tectum, the additional FL.1-positive cells are concentrated in the vicinity of degenerating retinal axons and their terminals. Most of the microglia in the injured optic nerve have amoeboid morphologies, and the foamy macrophages become depleted.

Animals↗

PubMed1993

The origin and nature of ramified and amoeboid microglia: a historical review and current concepts.

The origin of ramified microglia has been a longstanding controversial issue, with 4 major schools of thought, which state that they are derived (1) from invasion of mesodermal pial elements, (2) from neuroectodermal matrix cells together with the macroglia, (3) from pericytes, and (4) from invasion of monocytes in early development. This paper is in support of the last-mentioned hypothesis. It is known that ramified microglial cells do not divide under normal circumstances, and since our studies in the corpus callosum have shown that these cells do not appear until the fifth postnatal day, it is reasoned that they must be derived from some preexisting mitotically active cells. The putative precursor is the preponderant amoeboid microglia in the same region. Our experimental studies with the carbon labelling technique have demonstrated for the first time that blood monocytes invade into the early postnatal brain to become amoeboid microglia, which then differentiate into ramified microglia. Just like other tissue macrophages, the monocyte-derived amoeboid microglia exhibit features indicative of phagocytic activities. These include the content of hydrolytic enzymes, uptake of carbon, and a characteristic surface morphology, as seen by scanning electron microscopy. The transformation of amoeboid microglia into ramified microglia, which occurs between the second and third postnatal week, is considered to be a regressive phenomenon, as shown by the diminution of their content of hydrolytic enzymes and the downregulation of membrane antigen. Apart from their primary role as active phagocytes, their involvement in Alzheimer's disease (AD) is evidenced recently by the fact that the cells are specifically marked by antibodies present in the cerebrospinal fluid of AD patients. In conclusion, ramified microglial cells are derived from monocytes, but through an intermediate amoeboid microglia stage as active macrophages in the perinatal period.

Amoeba↗

PubMed1993

Detection of lysosomal cysteine proteinases in microglia: flow cytometric measurement and histochemical localization of cathepsin B and L.

The activation and differentiation of microglia is a prominent pathophysiological process in numerous inflammatory and demyelinating diseases of the central nervous system, including Alzheimer's disease and the AIDS encephalopathy. The tissue damage during these diseases has partly been attributed to lipid peroxidating reactive oxygen intermediates for which activated microglia are a major source. The destruction of tissue may also involve the release of proteolytic enzymes, such as the lysosomal cysteine proteinases cathepsin B and L, which are present notably in phagocytic cells. The cathepsins B and L are endopeptidases with a substrate specificity including important proteins, like myelin basic protein, extracellular matrix components, or the class II major histocompatibility complex. Because of this pathophysiological relevance the cathepsins B and L were chosen for histochemical demonstration in isolated and cultured rat microglia and measurement by a new flow cytometric method. Cathepsin B/L activity was measured flow cytometrically in single viable cells by the intracellular cleavage of non-fluorescent (Z-Phe-Arg)2-rhodamine 110 to the green fluorescent monoamide Z-Phe-Arg-rhodamine 110 and rhodamine 110. In microglia we measured a cathepsin B/L activity that was 2.5 times higher than in thioglycolate-elicited, i.e., inflammatory peritoneal rat macrophages. In elicited peritoneal macrophages the formation of fluorescent product was 6.2 times higher than in unstimulated resident peritoneal macrophages, demonstrating that the activation and differentiation of mononuclear phagocytes is accompanied by an increased cathepsin B/L enzyme activity. The subcellular localization of cathepsin B/L activity in plated viable microglia was demonstrated histochemically by the use of Z-Ala-Arg-Arg-4-methoxy-2-naphthylamide. Its blue fluorescent cleavage product 4-methoxy-2-naphthylamide was found in lysosomes. Our study shows that activated microglia are an important potential source of cathepsin B/L. This is particularly interesting as enzymatically active cathepsins have recently been found extracellularly at high levels in the senile plaques of Alzheimer's disease, which are known to contain many activated microglia. The release of proteinases by microglia may play a crucial role in the pathomechanism of tissue-destructing diseases in the brain.

Animals↗

PubMed1990

Chemotaxis by a CNS macrophage, the microglia.

Microglia demonstrate many characteristics similar to those seen in monocytes and tissue-specific macrophages, including phagocytosis, production of oxygen radicals, and growth factors and expression of MHC antigens. We have examined the ability of microglia, cultured from the cerebral cortices of neonatal rats, to demonstrate another important functional characteristic of monocytic-derived cells, that is, chemotaxis. Our results show that cultured rat microglia demonstrate chemotaxis to complement dependent chemoattractants such as recombinant C5a, zymosan activated serum, and to rat serum as well as to transforming growth factor-beta, a chemoattractant produced by platelets. Microglia fail to migrate to bacterial dependent chemoattractants such as the N-formyl peptides. The failure to respond is not dependent on maturational state of the microglia. Treatment with DMSO or casein, agents known to induce morphological and functional changes in cultured microglia reminescent of a "resting" and an "activated" macrophage, respectively, do not alter the response to fMet-Leu-Phe. In addition, the chemotactic response to serum in DMSO or casein-treated cells is the same as the response seen in untreated day 10 cultured microglia or untreated age-matched controls. The ability of microglia to migrate in response to inflammatory mediators suggests that these cells can move to sites of injury, thereby enabling them to participate in an inflammatory response.

Animals↗

PubMed1991

Application of lectin and B-lymphocyte-specific monoclonal antibodies for the demonstration of human microglia in formalin-fixed, paraffin-embedded brain tissue.

To evaluate the usefulness of microglial markers for routine neuropathological material, we studied formalin-fixed, paraffin-embedded human brain tissue with the immunoperoxidase method using the lectin Ricinus communis agglutinin (RCA-1) and four monoclonal antibodies (LN-1, LN-2, LN-3, anti-HLA-DR/alpha). RCA-1 stained resting microglia, but the staining intensity was mostly weak. LN-1 also stained resting microglia in paraffin sections first treated with protease. In contrast to LN-1, RCA-1 stained blood vessels heavily. LN-1 stained resting microglia more markedly than RCA-1 in brains fixed for a prolonged period of time. However, LN-1 recognized a small number of astrocytes in routine paraffin sections. LN-3 reactivity was detected on a few resting microglia, but was intensely expressed on large numbers of reactive microglia in many neurological diseases. Both LN-2 and anti-HLA-DR/alpha labelled microglia, but the reactions were inconsistent. This study suggests that the monoclonal antibodies LN-1 and LN-3 are useful for the demonstration of microglia in paraffin sections, and a combination of these antibodies and the antibody to glial fibrillary acidic protein is recommended in attempting to identify microglia.

Antibodies, Monoclonal↗

PubMed1990

Effects of colony stimulating factors on isolated microglia in vitro.

Effects of colony stimulating factors (CSF), known regulators for cells in monocytic lineage, on isolated microglia were examined. Interleukin-3 (IL-3) induced only morphological changes in rod-shaped microglia, while granulocyte-macrophage CSF (GM-CSF) and CSF-1 induced both morphological changes and proliferation of microglia. CSF-1 also activated the enzyme activity of microglia. These observations indicated that, in terms of regulation by cytokines, microglia are similar to mature cells in monocytic lineage. Although astrocytes reportedly produce IL-3 and GM-CSF, the effects of astrocyte-conditioned medium (Ast-Sup) were different from those of either IL-3 or GM-CSF. Ast-Sup caused ameboid microglia to become ramified, and did not induce proliferation of microglia. Factors from astrocytes may have a role in the transformation of microglia which occurs in either normal developing brain or inflammation in the brain.

Animals↗

PubMed1991

Isolation and characterization of human fetal brain-derived microglia in in vitro culture.

Human brain microglia may play a central role in immunopathogenesis of CNS diseases including HIV infection, multiple sclerosis and Alzheimer's disease. In order to investigate the possible relationship between microglia and the mononuclear phagocyte system, human brain microglia were isolated from 14-18-week-old fetal brains, and maintained in in vitro culture. Enriched fetal brain microglia were stained for different monocyte/macrophage and glial cell markers. Fresh dissociated brain cells lacked macrophage surface markers. Isolated microglial cells stained positive for complement receptor C3bi, Class II [human leukocyte antigen-DR (HLA-DR)] antigen and with the lectin Ricinus communis. Microglia also share several functional properties with monocyte/macrophages, which include generation of superoxide anion and histochemically demonstrable intracellular acid phosphatase and non-specific esterase. Primary human dissociated brain cultures were maintained in culture for at least 28 weeks. Although microglia were not observed above the astrocyte cell layer after 5 weeks in culture, microglia-like cells appear below the astrocyte layer after 12 weeks in culture. These cells stained positive for non-specific esterase and displayed oxidative burst activity upon activation with phorbol myristate acetate. Thus, we have successfully isolated an enriched population of microglia from human fetal brain and have demonstrated that these cells possess markers and properties which are characteristics of mononuclear phagocytes.

Acid Phosphatase↗

PubMed1988

A new immunoperoxidase marker for microglia in paraffin section.

We tested antisera against monocytic and lymphocytic lineages on 27 formalin-fixed, paraffin-embedded brains, obtained at autopsy, using the avidin-biotin-complex immunoperoxidase method. Patients ranged from one day to 69 years with 12 cases under the age of two. LN-1-positive microglia were present in 22 brains. LN-1 did not stain any other glial or neuronal cells. Five negative brains included two irradiated gliomas, two cases of multiple sclerosis and one normal case. Immunostaining was confined to cells with bipolar processes and rod-shaped nuclei recapitulating the characteristic features of microglia in silver-impregnated sections. LN-1-positive microglia were most prominent in the grey matter and in the grey-white junction with fewer positive cells seen in the white matter. Double immunostaining with LN-1 and glial fibrillary acidic protein (GFAP) clearly distinguished LN-1-positive microglia and GFAP-positive astrocytes. The expression of LN-1, a B-lymphocyte antigen, by microglia contradicts the macrophage derivation theory and supports data indicating a functional role of microglia in immune processes. LN-1, while not specific for microglia, should be considered a useful marker, more reliable than silver impregnation, for detecting microglia in paraffin section.

Adult↗