Ligand recognition by purified human mannose receptor

Kéry, Vladimír; Křepinský, Jiří J.; Warren, Christopher D.; Capek, Peter; Stahl, Philip D.

doi:10.1016/0003-9861(92)90092-b

Cited by 71 publications

(42 citation statements)

References 31 publications

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“…16 Although mannan significantly reduced ADAMTS13 uptake by macrophages, ADAMTS13 endocytosis seems to be only partly dependent on this C-type lectin, because its uptake by macrophages is not influenced by the presence of the blocking anti-MR antibody clone 15.2 or by the addition of D-mannose or GlcNAc, which interfere with binding of ligands to mannan-sensitive CLRs. 43 These data suggest that MMR does not play a major role in ADAMTS13 internalization by macrophages. We currently cannot exclude that, although it is unlikely, ADAMTS13 may bind to a site on MMR that is not blocked by clone 15.2.…”

Section: Discussionmentioning

confidence: 86%

The class I scavenger receptor CD163 promotes internalization of ADAMTS13 by macrophages

et al. 2017

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Key Points• Uptake of ADAMTS13 by macrophages is not dependent on the macrophage mannose receptor.• CD163 promotes internalization of ADAMTS13 by macrophages.Internalization of ADAMTS13 by macrophages may contribute to its clearance from the circulation. Here we investigated endocytic mechanisms that contribute to the uptake of ADAMTS13 by macrophages. Human monocyte-derived macrophages were used to monitor the uptake of fluorescently labeled recombinant ADAMTS13 by flow cytometry.Internalization of ADAMTS13 was blocked upon addition of the cell-permeable dynamin inhibitor dynasore. Partial blocking of ADAMTS13 uptake was observed by using mannan;however, uptake was not affected by an antibody that blocked binding to the macrophage mannose receptor CD206, which suggests that other endocytic receptors contribute to the internalization of ADAMTS13 by macrophages. A pull-down with ADAMTS13 and subsequent mass spectrometric analysis identified the class I scavenger receptor CD163 as a candidate receptor for ADAMTS13. Blocking experiments with monoclonal anti-CD163 antibody EDHu-1 resulted in decreased ADAMTS13 internalization by macrophages. Pronounced inhibition of ADAMTS13 uptake by EDHu-1 was observed in CD163 high-expressing macrophages. In agreement with these findings, CD163-expressing Chinese hamster ovary cells were capable of rapidly internalizing ADAMTS13. Surface plasmon resonance revealed binding of ADAMTS13 to scavenger receptor cysteine-rich domains 1-9 and 1-5 of CD163. Taken together, our data identify CD163 as a major endocytic receptor for ADAMTS13 on macrophages.

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Section: Discussionmentioning

confidence: 86%

The class I scavenger receptor CD163 promotes internalization of ADAMTS13 by macrophages

et al. 2017

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“…Mannan, D-mannose, and GlcNAc bind with different affinity to CLRs. 27 We observed a more pronounced inhibition of ADAMTS13 uptake when cells were pre-incubated with mannan ( Figure 3D). Mannan is a polysaccharide consisting of multiple mannose residues and therefore has a more than 100-fold higher affinity for mannan-sensitive CLRs compared to monomeric D-mannose.…”

mentioning

confidence: 75%

The macrophage mannose receptor promotes uptake of ADAMTS13 by dendritic cells

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Berg

et al. 2012

Blood

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ADAMTS13 is a plasma metalloproteinase that regulates platelet adhesion and aggregation by cleaving ultra-large VWF multimers on the surfaces of endothelial cells. Autoantibodies directed against ADAMTS13 prohibit the processing of VWF multimers, initiating a rare and lifethreatening disorder called acquired thrombotic thrombocytopenic purpura. The formation of autoantibodies depends on the activation of CD4 ؉ T cells. This process requires immune recognition, endocytosis, and subsequent processing of ADAMTS13 into peptides that are presented on MHC class II molecules to CD4 ؉ T cells by dendritic cells (DCs). In the present study, we investigated endocytosis of recombinant ADAMTS13 by immature monocyte-derived DCs using flow cytometry and confocal microscopy. After incubation of fluorescently labeled ADAMTS13 with DCs, significant uptake of ADAMTS13 was observed. Endocytosis of ADAMTS13 was completely blocked by the addition of EGTA and mannan. IntroductionAPCs continuously sample antigens from their environment and, after their processing, load antigen-derived peptides on MHC class I or II molecules for presentation to CD8 ϩ or CD4 ϩ T cells, respectively. To appropriately respond to incoming pathogens, APCs are equipped with a large diversity of cellsurface receptors, so-called pattern recognition receptors that recognize specific pathogen-associated molecular patterns. 1 This provides APCs such as dendritic cells (DCs) with the capacity to recognize a wide diversity of foreign pathogens. After encountering a pathogen, DCs undergo maturation and migrate to the draining lymph nodes, where they encounter and prime naive T cells. This mechanism ultimately generates a humoral response that is capable of rapidly neutralizing re-entering pathogens. It is well established that, in addition to recognizing pathogen-associated molecular patterns, pattern recognition receptors can also interact with molecular patterns present on endogenous proteins. 2 This results in the continuous presentation of "self-derived" peptides to CD4 ϩ T cells. 3 The efficient removal of potentially self-reactive T cells in the thymus prevents the stimulation of CD4 ϩ T cells by self-antigens presented on MHC class II molecules. Nevertheless, autoimmunity can develop as a result of activation of low-affinity CD4 ϩ T cells that have not been efficiently eliminated from the repertoire in the thymus. 4 In addition, shared T-cell epitopes between pathogen-encoded and self-antigens are a potential source for cross-reactive T cells. 5 The autoimmune disorder thrombotic thrombocytopenic purpura (TTP) results from the development of autoantibodies directed toward the metalloprotease ADAMTS13. 6 Several studies have shown that these Abs target an exposed surface in the spacer domain,which mediates binding of ADAMTS13 to its substrate, VWF. 6-13 Lack of cleavage of ultra-large VWF multimers by ADAMTS13 results in the accumulation of blood platelets at sites of vascular perturbation. 14 This promotes microvascular obstruction, resulting in low platelet...

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“…"I-Bolton-Hunter reagent was purchased from New England Nuclear (Boston, MA). A polyclonal rabbit antiserum generated against rat SP-D has been described previously (21 (52).…”

Section: Methodsmentioning

confidence: 99%

“…Protein-antibody complexes were precipitated using protein A-Sepharose, eluted with 1% SDS containing 5% /3-mercaptoethanol, and analyzed by SDS-PAGE as described previously (63). As a positive control, radiolabeled macrophage proteins were also immunoprecipitated using a polyclonal goat anti-mannose receptor antiserum, generously provided by Dr. Philip Stahl, or with nonimmune goat serum (52). For conditions using goat serum, protein G-Sepharose was substituted for protein A-Sepharose in an identical fashion.…”

Section: Methodsmentioning

confidence: 99%