Deletion of the murine scavenger receptor CD68

Song, Li; Lee, Carolyn; Schindler, Christian

doi:10.1194/jlr.m015412

Cited by 99 publications

(74 citation statements)

References 44 publications

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“…Therefore, a lower expression of this molecule specifically in these APC populations would be consistent with a reduced ability to ingest myelin-derived lipids. Mononuclear phagocytes from CD68 −/− mice have been shown to exhibit a trend toward enhanced antigen presentation to CD4 + T cells (55), similar to the trend we observed in APCs in IFN-γ-signaling-deficient mice during EAE. Additionally, GM-CSF has been shown to cause monocytes to increase ROS production and decrease phagocytosis (56).…”

Section: Discussionsupporting

confidence: 68%

IFN-γ ameliorates autoimmune encephalomyelitis by limiting myelin lipid peroxidation

Sosa

Murphey

Robinson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Evidence has suggested both a pathogenic and a protective role for the proinflammatory cytokine IFN-γ in experimental autoimmune encephalomyelitis (EAE). However, the mechanisms underlying the protective role of IFN-γ in EAE have not been fully resolved, particularly in the context of CNS antigen-presenting cells (APCs). In this study we examined the role of IFN-γ in myelin antigen uptake by CNS APCs during EAE. We found that myelin antigen colocalization with APCs was decreased substantially and that EAE was significantly more severe and showed a chronic-progressive course in IFN-γ knockout (IFN-γ −/− ) or IFN-γ receptor knockout (IFN-γR −/− ) mice as compared with WT animals. IFN-γ was a critical regulator of phagocytic/activating receptors on CNS APCs. Importantly, "free" myelin debris and lipid peroxidation activity at CNS lesions was increased in mice lacking IFN-γ signaling. Treatment with N-acetyl-L-cysteine, a potent antioxidant, abolished lipid peroxidation activity and ameliorated EAE in IFN-γ-signalingdeficient mice. Taken together the data suggest a protective role for IFN-γ in EAE by regulating the removal of myelin debris by CNS APCs and thereby limiting the substrate available for the generation of neurotoxic lipid peroxidation products.

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Section: Discussionsupporting

confidence: 68%

IFN-γ ameliorates autoimmune encephalomyelitis by limiting myelin lipid peroxidation

Sosa

Murphey

Robinson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Finally, CD68-deficient DCs demonstrated normal capacity to present antigens and induce humoral immune responses. 54 Altogether, the findings of Song et al 54 suggest no apparent role Figure 2 The β-strand arrangement of the DC-LAMP domain. The 'front' and 'back' β-sheets are drawn in red and blue, respectively.…”

Section: Cd68: a Role In Inflammation And Immunitymentioning

confidence: 87%

“…Inhibition of macrosialin did not affect the binding of oxLDL to macrophages. 53 Song et al 54 reported that CD68-deficient mononuclear phagocytes showed a potent lipid uptake thereby indicating no significant role of murine CD68 in lipid internalization. Indeed, more recent studies disputed the involvement of CD68 in atherogenic foam cell formation.…”

Section: Cd68 Function: Does Cd68 Contribute To Athero-sclerosis and mentioning

confidence: 99%

“…Song et al 54 comprehensively assessed immune and inflammatory properties of CD68-deficient murine myeloid cells. Like wild-type macrophages, CD68-lacking mouse macrophages exhibited normal phagocytic activity towards killed bacteria Staphylococcus aureus and failed to show defective innate response to infection by Listeria monocytogenes, Legionella pneumophila, and vesicular stomatitis virus.…”

Section: Cd68: a Role In Inflammation And Immunitymentioning

confidence: 99%

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CD68/macrosialin: not just a histochemical marker

Chistiakov

Killingsworth

Myasoedova

et al. 2017

Laboratory Investigation

523

330

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CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells. Cell-specific CD68 expression and differentiated expression levels are determined by the complex interplay between transcription factors, regulatory transcriptional elements, and epigenetic factors. Human CD68 and its mouse ortholog macrosialin belong to the family of LAMP proteins located in the lysosomal membrane and share many structural similarities such as the presence of the LAMP-like domain. Except for a second LAMP-like domain present in LAMPs, CD68/microsialin has a highly glycosylated mucin-like domain involved in ligand binding. CD68 has been shown to bind oxLDL, phosphatidylserine, apoptotic cells and serve as a receptor for malaria sporozoite in liver infection. CD68 is mainly located in the endosomal/lysosomal compartment but can rapidly shuttle to the cell surface. However, the role of CD68 as a scavenger receptor remains to be confirmed. It seems that CD68 is not involved in binding bacterial/viral pathogens, innate, inflammatory or humoral immune responses, although it may potentially be involved in antigen processing/presentation. CD68 could be functionally important in osteoclasts since its deletion leads to reduced bone resorption capacity. The role of CD68 in atherosclerosis is contradictory.

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“…In addition to manual counting, myeloid cell subsets can be identified to some extent by the immunohistochemical examination of lung sections, which allows for analyses based on the anatomical locations and expressions of specific markers. Unfortunately, the expression of some commonly used markers is not restricted to myeloid cells, and others may overlap in different myeloid cell subsets (2)(3)(4)(5). As a result, the immunohistochemical identification of lung myeloid subpopulations may be not sufficiently specific.…”

mentioning

confidence: 99%

Identification of Myeloid Cell Subsets in Murine Lungs Using Flow Cytometry

Zaynagetdinov

Sherrill

Kendall

et al. 2013

Am J Respir Cell Mol Biol

222

220

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Although the antibody-based recognition of cell-surface markers has been widely used for the identification of immune cells, overlap in the expression of markers by different cell types and the inconsistent use of antibody panels have resulted in a lack of clearly defined signatures for myeloid cell subsets. We developed a 10-fluorochrome flow cytometry panel for the identification and quantitation of myeloid cells in the lungs, including pulmonary monocytes, myeloid dendritic cells, alveolar and interstitial macrophages, and neutrophils. After the initial sorting of viable CD451 leukocytes, we detected three leukocyte subpopulations based on CD68 expression: CD68 /CD11b1 /Gr1 hi ). The validity of cellular signatures was confirmed by a morphological analysis of FACS-sorted cells, functional studies, and the depletion of specific macrophage subpopulations using liposomal clodronate. We believe our approach provides an accurate and reproducible method for the isolation, quantification, and characterization of myeloid cell subsets in the lungs, which may be useful for studying the roles of myeloid cells during various pathological processes.Keywords: interstitial macrophages; alveolar macrophages; monocytes; myeloid dendritic cells; neutrophilsThe heterogeneous population of myeloid cells in the lungs is important for maintaining homeostasis and regulating inflammation, injury, and remodeling. These cells are thought to originate from bone marrow-derived precursors, and they differentiate into mature cells with a variety of functional properties, depending on environmental cues. Multiple studies have demonstrated functional and phenotypic differences between myeloid cell subsets, including monocytes, myeloid dendritic cells, macrophages, and neutrophils. However, the specific identification and quantification of subsets of these cells in tissues are complex, and a comprehensive scheme for isolating these cells from the lungs is not readily available. To date, studies of lung myeloid cells have been limited by the inconsistent use of cellular markers and a lack of clearly defined signatures for these cells, resulting in difficulties comparing studies from different laboratories and generalizing findings across different model systems. Therefore, we undertook a study to identify and quantify myeloid cell populations comprehensively in the lungs, using flow cytometry.Based on the recent explosion of information regarding the mechanisms that underpin innate immune responses, a clear need is apparent for better strategies to identify and study myeloid cell subpopulations in the lungs. The traditional method for the identification and quantification of lung myeloid cells involves the manual counting of cells obtained from the airways by bronchoalveolar lavage (BAL). This methodology normally yields a predominance of alveolar macrophages, because these are the primary immune cells in the airspaces. Interstitial macrophages, however, comprise a substantial portion of the lung myeloid cell population (1), and may have dif...

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Deletion of the murine scavenger receptor CD68

Cited by 99 publications

References 44 publications

IFN-γ ameliorates autoimmune encephalomyelitis by limiting myelin lipid peroxidation

IFN-γ ameliorates autoimmune encephalomyelitis by limiting myelin lipid peroxidation

CD68/macrosialin: not just a histochemical marker

Identification of Myeloid Cell Subsets in Murine Lungs Using Flow Cytometry

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