5D4 keratan sulfate epitope identifies a subset of ramified microglia in normal central nervous system parenchyma

Bertolotto, Antonio; Agresti, Cristina; Castelló, Anna; Manzardo, E.; Riccio, A.

doi:10.1016/s0165-5728(97)00251-8

Cited by 29 publications

(19 citation statements)

References 35 publications

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“…KS was first identified in bovine cornea in 1953 (32) and was later shown to be expressed in cartilage, bone, and the central nervous system (19). In fact, KS is expressed on a subpopulation of microglia (33) and spinal cord (34). Interestingly, KS synthesis is up-regulated in the lesions on central nervous system injury (35).…”

Section: Discussionmentioning

confidence: 99%

Dual Specificity of Langerin to Sulfated and Mannosylated Glycans via a Single C-type Carbohydrate Recognition Domain

Tateno

Ohnishi

Yabe

et al. 2010

Journal of Biological Chemistry

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Langerin is categorized as a C-type lectin selectively expressed in Langerhans cells, playing roles in the first line of defense against pathogens and in Birbeck granule formation. Although these functions are thought to be exerted through glycan-binding activity of the C-type carbohydrate recognition domain, sugar-binding properties of Langerin have not been fully elucidated in relation to its biological functions. Here, we investigated the glycan-binding specificity of Langerin using comprehensive glycoconjugate microarray, quantitative frontal affinity chromatography, and conventional cell biological analyses. Langerin showed outstanding affinity to galactose-6-sulfated oligosaccharides, including keratan sulfate, while it preserved binding activity to mannose, as a common feature of the C-type lectins with an EPN motif. By a mutagenesis study, Lys-299 and Lys-313 were found to form extended binding sites for sulfated glycans. Consistent with the former observation, the sulfated Langerin ligands were found to be expressed in brain and spleen, where the transcript of keratan sulfate 6-O-sulfotransferase is expressed. Moreover, such sulfated ligands were up-regulated in glioblastoma relative to normal brain tissues, and Langerin-expressing cells were localized in malignant brain tissues. Langerin also recognized pathogenic fungi, such as Candida and Malassezia, expressing heavily mannosylated glycans. These observations provide strong evidence that Langerin mediates diverse functions on Langerhans cells through dual recognition of sulfated as well as mannosylated glycans by its uniquely evolved C-type carbohydrate-recognition domain.

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Section: Discussionmentioning

confidence: 99%

Dual Specificity of Langerin to Sulfated and Mannosylated Glycans via a Single C-type Carbohydrate Recognition Domain

Tateno

Ohnishi

Yabe

et al. 2010

Journal of Biological Chemistry

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“…Rodent macrophages may not be excluded from GLUT5 staining. On the other hand, antibodies against the keratin sulfate epitope 5D4 can serve such discrimination in the rat (54).…”

Section: B Identificationmentioning

confidence: 99%

Physiology of Microglia

Kettenmann

Hanisch

Нода

et al. 2011

Physiological Reviews

3,144

2,981

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Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed “resting microglia.” Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the “activated microglial cell.” This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

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“…It is however difficult to reliably differentiate microglia from macrophages by immunocytochemistry. The 5D4 antibody against keratan sulfate epitope has been for example shown to detect only microglia and not macrophages in rat tissue [105,106]. Many studies used the term microglia, macrophages or microglia/macrophages to describe potentially mixed cell populations.…”

Section: Contribution Of Myeloid Cells To Brain Tumorsmentioning

confidence: 99%

Tumor Microenvironment in the Brain

Lorger

2012

Cancers

103

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In addition to malignant cancer cells, tumors contain a variety of different stromal cells that constitute the tumor microenvironment. Some of these cell types provide crucial support for tumor growth, while others have been suggested to actually inhibit tumor progression. The composition of tumor microenvironment varies depending on the tumor site. The brain in particular consists of numerous specialized cell types such as microglia, astrocytes, and brain endothelial cells. In addition to these brain-resident cells, primary and metastatic brain tumors have also been shown to be infiltrated by different populations of bone marrow-derived cells. The role of different cell types that constitute tumor microenvironment in the progression of brain malignancies is only poorly understood. Tumor microenvironment has been shown to be a promising therapeutic target and diagnostic marker in extracranial malignancies. A better understanding of tumor microenvironment in the brain would therefore be expected to contribute to the development of improved therapies for brain tumors that are urgently required due to a poor availability of treatments for these malignancies. This review summarizes some of the known interactions between brain tumors and different stromal cells, and also discusses potential therapeutic approaches within this context.

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5D4 keratan sulfate epitope identifies a subset of ramified microglia in normal central nervous system parenchyma

Cited by 29 publications

References 35 publications

Dual Specificity of Langerin to Sulfated and Mannosylated Glycans via a Single C-type Carbohydrate Recognition Domain

Dual Specificity of Langerin to Sulfated and Mannosylated Glycans via a Single C-type Carbohydrate Recognition Domain

Physiology of Microglia

Tumor Microenvironment in the Brain

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