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Results for “perivascular macrophages”

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At least 19 recordsLinked to original sources
PubMed2026

Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in mouse and human.

Brain perivascular macrophages maintain brain physiology, yet their transcriptional regulators and functions in health and disease remain unclear. Using single-cell multi-omics and functional experiments, we identify cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) as a key transcription factor for brain perivascular macrophages, and conditional deletion of cMAF disrupts their phenotype in vivo. Functionally, cMAF drives insulin-like growth factor-1 (IGF1) expression in perivascular macrophages, enabling communication with endothelial cells. Consistently, cMAF deletion in perivascular macrophages causes transcriptional alterations in cerebral arteries, affecting vascular functions. Notably, cMAF emerges as the main transcription factor for human perivascular macrophages, suggesting conservation of this transcriptional module. During Alzheimer's disease (AD), human perivascular macrophages upregulate cMAF and IGF1 to enhance communication with vascular cells, and this response is abrogated in APOE4 carriers. Lastly, we explore an uncharacterized polymorphism in cMAF, providing evidence that the cMAF program is protective against AD. Targeting cMAF in perivascular macrophages may offer new therapeutic strategies for neurodegenerative and cerebrovascular diseases.

APOE4↗
PubMed2026

Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer's disease.

Myeloid cells, including microglia and perivascular macrophages, are central to Alzheimer's disease (AD) neurobiology, yet their role remains incompletely understood. We profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 donors spanning the lifespan and showing varying degrees of AD neuropathology. We delineated six subclasses comprising 13 transcriptionally distinct subtypes and identified adaptive changes associated with aging and AD progression. Here we show that a disease-associated microglial subtype, characterized by elevated GPNMB expression and enriched for polygenic AD risk, expands with AD pathology and shows increased phagocytic activity. We identify MITF as an upstream regulator required to maintain this microglial state. Cell-cell interaction analyses prioritize APOE-SORL1 and APOE-TREM2 signaling pairs associated with disease progression. Using human and mouse models, we demonstrate that the neuroprotective effects of this microglial subtype depend on TREM2. These findings provide mechanistic insights into myeloid cell function in aging and AD, aiding therapeutic discovery.

Humans↗
PubMed2024

Plasticity of Human Microglia and Brain Perivascular Macrophages in Aging and Alzheimer's Disease.

The complex roles of myeloid cells, including microglia and perivascular macrophages, are central to the neurobiology of Alzheimer's disease (AD), yet they remain incompletely understood. Here, we profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 unique donors covering the human lifespan and varying degrees of AD neuropathology. We delineated 13 transcriptionally distinct myeloid subtypes organized into 6 subclasses and identified AD-associated adaptive changes in myeloid cells over aging and disease progression. The GPNMB subtype, linked to phagocytosis, increased significantly with AD burden and correlated with polygenic AD risk scores. By organizing AD-risk genes into a regulatory hierarchy, we identified and validated MITF as an upstream transcriptional activator of GPNMB, critical for maintaining phagocytosis. Through cell-to-cell interaction networks, we prioritized APOE-SORL1 and APOE-TREM2 ligand-receptor pairs, associated with AD progression. In both human and mouse models, TREM2 deficiency disrupted GPNMB expansion and reduced phagocytic function, suggesting that GPNMB's role in neuroprotection was TREM2-dependent. Our findings clarify myeloid subtypes implicated in aging and AD, advancing the mechanistic understanding of their role in AD and aiding therapeutic discovery.

Journal Article↗
PubMed1978

Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis.

Perivascular cells in CNS tissue from six multiple sclerosis (MS) patients and a patient with motor neuron disease were examined by light and electron microscopy. Lymph node tissue from one MS patient was also examined. CNS perivascular macrophages in both MA and motor neuron disease were found to closely resemble free macrophages elsewhere in the body except that they often contained unusually large primary lysosomes. Cytoplasmic inclusions consisting of membrane-bound stacks of curved linear profiles, presumed to be a product of myelin degradation, were constantly observed in microglia in MS plaques but were rarely observed in perivascular macrophages in the same area. Unidentified cylindrical bodies were observed within cysternae of rough endoplasmic reticulum in some lymph node cells. Quantitative studies of the perivascular cell population in one MS case revealed, in histologically normal white matter 260 lymphocytes and 178 plasma cells per cubic millimeter of fresh tissue. Typical chronic plaque tissue without obvious inflammatory cell cuffing contained 1772 plasma cells per cubic millimeter of fresh tissue. No plasma cells were observed in the CNS in motor neuron disease. The results of this study suggest that perivascular macrophages in the CNS represent a specialized population of monocyte-derived free macrophages, that these cells differ functionally from microglial cells, and that the digestion of myelin breakdown products in MS requires the participation of both cell types. The results also suggest that in some chronic MS cases there is a large, permanent population of CNS plasma cells that persists, like the elevated cerebrospinal fluid IgG level in this disease, for the life of the patient, that these cells, rather than inflammatory cells in fresh lesions, are the major source of this raised IgG, and that the existence of such a population of cells may indicate the continuing expression of antigens in chronic MS lesions in the absence of fresh lesion formation.

Adult↗
PubMed1975

Cell population dynamics of periodontal ligament stimulated with parathyroid extract.

Young adult rats were injected with parathyroid extract (PTE). Periodontal ligament (PDL) adjacent to a previously resorbing alveolar bone surface was divided into four zones number I to IV, from bone to cementum. Zones I and IV were within 25 mmu of the bone and cementum surfaces, respectively, while a line bisecting the center of the PDL separated Zones II and III. A net increase of about 16 total nuclei in all zones was observed during the first five hours after PTE administration. Since local mitosis accounted for no more than two nuclei, approximately 14 cells apparently migrated into the area. Over the first five hours Zones I and II combined showed a 21-cell increase, being apparently the sole recipients of cells migrating into the field (14) plus approximately seven more from Zone III, which lost cells during the time period. The concurrent histological observation in Zone II, of increased intravascular monocytes and perivascular macrophages during the first five hours, suggests cells are migrating into Zone II via vascular channels. The data suggest two sources for increased PDL cellularity associated with stimulated osteoclast histogenesis: (1) local PDL cellular proliferation and (2) influx of migrating cells (probably through vascular channels) during first five hours after PTE.

Animals↗
PubMed1977

Ultrahistochemical analysis of glycosaminoglycan hydrolysis in the rat periodontal ligament. II. Aryl sulfatase and bone resorption.

The distribution of aryl sulfatase in the rat periodontal ligament was investigated by ultrastructural histochemistry. In the periodontal ligament aryl sulfatase was localized specifically in osteoclasts and in vicinal perivascular macrophages. Macrophages associated with bone formation did not stain. The authors interpret this specificity as a potential marker for osteoclast differentiation from macrophages--or as a further indication of the capacity of macrophages to modulate their enzymatic complement in response to the environment. To explain the absence of aryl sulfatase in areas of bone formation we suggest that different sulfate esters are mobilized from resorbing and mineralizing matrices, and that only the enzyme associated with bone resorption is histochemically detectable with the artificial substrates currently used.

Animals↗
PubMed1978

The exocrine pancreas in triamcinolone-treated mice. A light and electron microscopy study.

6-week-old ICR strain female mice were given between 16 and 21 daily injections of the synthetic glucocorticoid, triamcinolone diacetate (8 mg/kg body weight). Portions of their pancreas were examined by light and electron microscopy and compared with untreated littermate controls. Despite marked variability from animal to animal and lobule to lobule, triamcinolone treatment induced increased zymogen depletion and also the development of large basal vacuoles in many acinar cells. At the ultrastructural level, acinar cells show pronounced mitochondrial swelling, which in many instances is accompanied by the development of myelin whorls. The number of cells with distended granular endoplasmic reticulum is increased as is the number of atrophying cells and cells apparently undergoing disintegration. In addition, there are indications of marked activation of interlobular perivascular macrophages which show marked vacuolation. Our observations suggest that pancreatic acinar cells show cytological changes as a result of experimental hypercorticoidism.

Animals↗
PubMed1977

Ultrastructural analysis of glycosaminoglycan hydrolysis in the rat periodontal ligament. I. Evidence for macrophage involvement in bone remodelling.

We identified the cellular sites of glycosaminoglycan hydrolysis by localizing a key enzyme, N-acetyl-beta-glucosaminidase, in the rat periodonatal ligament. Reaction product was seen in osteoclasts, osteoblasts, fibroblasts, and in macrophages situated perivascularly in areas of bone remodelling. The preferential location of macrophages in areas of both bone formation and bone resorption, and their intense NAGase activity identified the macrophage as a significant participant in the total process of bone remodelling. We considered the presence of reaction product in the Golgi zone and the rough endoplasmic reticulum of osteoblasts and fibroblasts as possible localization of a NAG-transferase.

Acetylglucosaminidase↗
PubMed1977

[Experimental allergic pulpitis in rabbits].

Ten male, albino rabbits, weighing about 2,5 kg, were sensitized with 0.05% of 1-chloro-2,4-dinitrobenzene (DNCB) in complete Freund's adjuvant. Ten controls received the complete Freund's adjuvant only. Fourteen days later, the animals were submitted to a dental test. The four incisor pulps were exposed under general anesthesia. A sterile cotton pellet with 10-(-4) mg of DNCB was sealed inside the cavity. A skin test was also performed with 0.1% DNCB. The operative trauma was evaluated on five additional control animals. Twenty four hours after the challenge, the animals were killed and their teeth were studied histologically. Three different pulpitis were observed: 1) in animals without DNCB, a traumatic pulpitis with a mild focal necrosis and serous infiltrate; 2) a toxic pulpitis induced by the DNCB in the controls. They were killed and their teeth were studied histologically. Three different kinds of pulpitis induced in sensitized animals. A considerable necrosis is present close to the pulp exposure. This pulpitis is characterized by a marked serous exudate and by an accumulation of lymphocytes, eosinophils and macrophages, either perivascularly or in the pulpal mesenchyme. A modification of the present classification of pulpitis is proposed.

Animals↗
PubMed1979

The response of rat bronchus-associated lymphoid tissue to local antigenic challenge.

Single doses of antigen suspension (alum-precipitated canine serum proteins) were administered intratracheally to SPF rats. After periods of 1, 2 and 3 weeks rats were killed and their lungs examined histologically. After an initial macrophage and perivascular lymphoid reaction, dose-related increases were found in the amount of bronchus-associated lymphoid tissue (BALT) and in the amount of DNA within BALT cells, indicating increased cell division. Immunoglobulin-containing cells were demonstrated within BALT 3 weeks after the exposure to antigen. A prominent and extensive bronchial lympho-epithelium was seen overlying BALT follicles in antigen-treated rats, while in control animals the respiratory epithelium overlying BALT was predominantly normal ciliated epithelium. The significance of these findings is discussed in the light of the possible defensive role of BALT in cases of respiratory disease of man and animals.

Animals↗
PubMed1978

Macrophages migration through the brain parenchyma to the perivascular space following particle ingestion.

Forty-eight rats received intracerebral injections of sterile colloidal carbon. At intervals between 10 minutes and 31 days after carbon injection, the rats were perfused with glutaraldehyde, and autopsies were performed. Between 10 minutes and 3 hours after injection, carbon particles were extracellular and located strictly within the needle track. During the first few days the carbon was ingested by macrophages. Initially absent, carbon-laden macrophages spread to the neuropil immediately surrounding the injection site at 7 to 31 days following injection. These carbon-laden macrophages frequently were elongated within the neuropil and resembled microglia. Carbon-laden macrophages eventually accumulated around local vessels and in perivascular spaces. Many macrophages containing carbon remained in the injection site at the longest sampling interval of 31 days. Results indicate two macrophage responses to colloidal carbon in the central nervous system: a) an indolent population remains in the injection site for at least 1 month and b) a second population of macrophages emigrates through the neuropil. They eventually surround local vessels and enter the perivascular space. The migrating macrophages offer an explanation for the peculiar perivascular cells in Krabbe's disease and may provide a link between the CNS parenchyma and immunocompetent cells.

Animals↗
PubMed1978

The distribution of myelin basic protein in central nervous system lesions of multiple sclerosis and acute experimental allergic encephalomyelitis.

To obtain more information about early events in central nervous system myelin injury in multiple sclerosis (MS), a comparative study was conducted of the distribution of myelin basic protein (BP) in tissue lesions of both MS and experimental allergic encephalomyelitis (EAE). Sixteen postmortem specimens containing lesions from 4 persons with MS and the brains of 14 guinea pigs with acute EAE induced with BP were studied. Cryostat sections of quick-frozen material were fixed, treated with rabbit antibody to BP, and processed by immunoperoxidase techniques. The reaction of antibody to BP was reduced or absent in MS lesions but normal in uninvolved surrounding tissue. Alterations in BP generally paralleled changes in staining of myelin by histological methods. Marked diminution of reactivity with anti-BP occurred in early lesions of MS and extended far beyond any identifiable inflammatory elements. In both parenchyma and perivascular areas, lipid-laden macrophages in MS plaques frequently contained BP material in addition to a variable amount of endogenous peroxidatic activity. Compared with MS, BP was relatively well preserved in brains of guinea pigs with EAE. At the light microscopy level, normal-appearing patterns of BP existed adjacent to the perivascular cellular infiltrates, and macrophages containing BP material were rare. The results of this study suggest differences between MS and acute EAE in both removal of BP from the central nervous system and its subsequent disposal.

Acute Disease↗
PubMed1975

[Blood vessels of the hypophysis].

The construction of the intraorganic vessels of the hypophysis was studied by different injectional methods in cats and partly in dogs. The obtained data confirmed the portal microcirculation in the hypophysis of the animals under investigation. Anatomical and some experimental data speak in favour of the blood flow direction in the portal system from the medial eminence towards the anterior part of the adenohypophysis. The capillaries of the portal system were demonstrated to anastomose with arcuate nucleus of the hypothalamus and with the caudal parts of the neurohypophysis. The experiments with intravital accumulation of the trypan blue revealed macrophagal activity of the perivascular connective tissue elements of the portal system. An attempt was made to objectively analyze the capillary architectonics of the hypophysis portal system. The obtained data on its peculiar features are discussed in connection with the capillary construction and peculiarities of the metabolism of the hypothalmic neurosecretory nuclei.

Animals↗
PubMed1975

Intranuclear "paramyxovirus-like" material in multiple sclerosis, adreno-leukodystrophy and Kuf's disease.

Detailed comparative ultrastructural examination of multiple sclerosis (MS) plaques, inflammatory CNS lesions from adreno-leukodystrophy(A-LD), tissue from a case of chronic granulomatous meningitis, biopsy samples of necrotic cerebral cortex and CNS tissue from a case of Kuf's disease (adult-type ceroid lipofuscinosis), has revealed that the intranuclear filamentous material previously thought to be related to a viral infection in MS is a non-specific finding. These intranuclear strands were, however, found in greatest frequency in the acute lesions of MS and were absent from chronically demyelinated areas. The macrophages, lymphocytes and fibrocytes containing filamentous material in the nuclei were mainly perivascular. In A-LD, some macrophages in active lesions contained similar nuclei, and in Kuf's disease they were present in some glial cells in the cerebral cortex.

Acute Disease↗
PubMed1977

Hapten-specific delayed hypersensitivity to epsilon-2,4-dinitrophenyl-L-lysine-Ficoll in guinea pigs immunized with 2,4-dinitrophenyl-keyhole limpet hemocyanin.

After active immunization with 2,4-dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH), 2,4-dinitropheynl-L-lysine (DNPL)-Ficoll may elicit indurated, erythematous skin reactions lasting 24-72 h. Histological sections of these reactions, examined by microscope techniques, showed they contained polymorphonuclear leukocytes and perivascularly situated lymphocytes and macrophages, but had very few basophils. Consequently, the reaction was interpreted as having an immediate component and a component typical of delayed hypersensitivity; this indicated that the delayed reaction could be specific for the DNP hapten. Although this delayed type of skin reaction was not transferred to recipients with anti-DNP-KLH serum, one pool of that serum did sensitize guinea pigs so that they could respond with a different skin reaction after challenge with DNPL-Ficoll. This reaction was soft, pale pink, and lasted for 24 h. Histologically, it contained only a few polymorphonuclear leukocytes. It differed from the delayed reaction in actively immunized animals in that it lacked induration, and was devoid of lymphocytes and macrophages.

Animals↗
PubMed1978

Electron microscopical studies on onchocerciasis. I. Mesenchyme reaction in untreated onchocercal dermatitis and ultrastructure of the microfilariae.

Skin biopsies of 22 untreated Liberian patients suffering from onchocercal dermatitis were studied by electron microscopy. The microfilariae tend to accumulate in the upper dermis, without eliciting a cellular reaction. Occasionally macrophages or mast cells are found in the neighbourhood of the microfilariae. The most conspicuous changes concern the presence of perivascular infiltrates, comprised of lymphocytes and macrophages, with a varying admixture of plasma cells. Only exceptionally the macrophages show an increase in number and size of their lysosomes and pseudopodia as well as prominent strands of ergastoplasm indicating an activation. The endothelial walls of the dermal vessels are swollen. The amount of mast cells in the upper dermis is increased. Ultrastructural features of the microfilariae are described, especially the cuticle, muscles, central undifferentiated cells and cephalic region. When comparing these findings with the literature on the fine structural morphology of the Latinamerican form, no differences can be found.

Adolescent↗
PubMedDate not supplied

Transverse myelitis in mixed connective tissue disease.

Neurologic disease is reported to occur in just 10% of patients with mixed connective tissue disease (MCTD). Most commonly, this is manifested by mild trigeminal neuralgia. This report details the clinical and neuropathologic findings of transverse myelitis in a patient with MCTD. Neurologic features include progressive areflexic paraplegia with loss of bowel and bladder function. Neuropathologically there was thinning of the thoracic cord, widespread loss of axons and myelin sheaths, reactive astrocytosis, macrophage formation, vascular thickening with perivascular chronic inflammatory cell infiltration, and calcium deposits. This case demonstrates that severe neurologic disease unresponsive to therapy can occur in MCTD.

Adult↗