{"doi":"10.1002/hep.510260531","title":"Cluster mannosides can inhibit mannose receptor-mediated tissue-type plasminogen activator degradation by both rat and human cells","abstract":"<jats:sec>\n            <jats:title/>\n            <jats:p>Recently, we developed a series of cluster mannosides that were able to inhibit tissue-type plasminogen activator (t-PA) binding to the isolated mannose receptor. The mannoside with the highest affinity was able to inhibit t-PA clearance by the liver in the rat. To test whether these mannosides would also be efficient inhibitors in humans, we studied the expression of the mannose receptor in the human liver and determined the efficacy of the mannosides to inhibit mannose receptor-mediated t-PA degradation by both rat and human cells. Immunohistochemistry indicates that, like the rat, human liver endothelial cells and human Kupffer cells do express the mannose receptor. The mannosides do inhibit mannose receptor-mediated t-PA binding, association, and degradation by isolated rat liver endothelial cells and t-PA association and degradation by cultured human macrophages at similar concentrations. The cluster mannoside with six mannose residues connected with a backbone of five lysine groups (M<jats:sub>6</jats:sub>L<jats:sub>5</jats:sub>) was, like unlabeled t-PA, able to inhibit <jats:sup>125</jats:sup>I-t-PA degradation in the nmol/L range, while the mannoside M<jats:sub>5</jats:sub>L<jats:sub>4</jats:sub> inhibited <jats:sup>125</jats:sup>I-t-PA degradation in the μmol/L range. The concentrations of mannoside necessary to inhibit <jats:sup>125</jats:sup>I-t-PA degradation <jats:italic toggle=\"yes\">in vitro</jats:italic> were comparable with the concentrations necessary to inhibit mannose receptor-mediated <jats:sup>125</jats:sup>I-t-PA clearance <jats:italic toggle=\"yes\">in vivo</jats:italic>. We conclude that there is no species difference between rat and humans with respect to the distribution of the mannose receptor in the liver and the affinity of the cluster mannosides, establishing the relevance of the inhibition of mannose receptor- mediated t-PA clearance by M<jats:sub>6</jats:sub>L<jats:sub>5</jats:sub> as observed in the rat, for the human situation.</jats:p>\n          </jats:sec>","journal":"Hepatology","year":1997,"id":640624,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1665021,"name":"M M Barrett-Bergshoeff","orcid":null,"position":1,"is_corresponding":false},{"id":1665022,"name":"E A L Biessen","orcid":null,"position":2,"is_corresponding":false},{"id":1665023,"name":"E van de Bilt","orcid":null,"position":3,"is_corresponding":false},{"id":1665024,"name":"T J C van Berkel","orcid":null,"position":4,"is_corresponding":false},{"id":1665025,"name":"D C Rijken","orcid":null,"position":5,"is_corresponding":false},{"id":1665020,"name":"F Noorman","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Cluster mannosides can inhibit mannose receptor-mediated tissue-type plasminogen activator degradation by both rat and human cells","abstract":"<jats:sec>\n            <jats:title/>\n            <jats:p>Recently, we developed a series of cluster mannosides that were able to inhibit tissue-type plasminogen activator (t-PA) binding to the isolated mannose receptor. The mannoside with the highest affinity was able to inhibit t-PA clearance by the liver in the rat. To test whether these mannosides would also be efficient inhibitors in humans, we studied the expression of the mannose receptor in the human liver and determined the efficacy of the mannosides to inhibit mannose receptor-mediated t-PA degradation by both rat and human cells. Immunohistochemistry indicates that, like the rat, human liver endothelial cells and human Kupffer cells do express the mannose receptor. The mannosides do inhibit mannose receptor-mediated t-PA binding, association, and degradation by isolated rat liver endothelial cells and t-PA association and degradation by cultured human macrophages at similar concentrations. The cluster mannoside with six mannose residues connected with a backbone of five lysine groups (M<jats:sub>6</jats:sub>L<jats:sub>5</jats:sub>) was, like unlabeled t-PA, able to inhibit <jats:sup>125</jats:sup>I-t-PA degradation in the nmol/L range, while the mannoside M<jats:sub>5</jats:sub>L<jats:sub>4</jats:sub> inhibited <jats:sup>125</jats:sup>I-t-PA degradation in the μmol/L range. The concentrations of mannoside necessary to inhibit <jats:sup>125</jats:sup>I-t-PA degradation <jats:italic toggle=\"yes\">in vitro</jats:italic> were comparable with the concentrations necessary to inhibit mannose receptor-mediated <jats:sup>125</jats:sup>I-t-PA clearance <jats:italic toggle=\"yes\">in vivo</jats:italic>. We conclude that there is no species difference between rat and humans with respect to the distribution of the mannose receptor in the liver and the affinity of the cluster mannosides, establishing the relevance of the inhibition of mannose receptor- mediated t-PA clearance by M<jats:sub>6</jats:sub>L<jats:sub>5</jats:sub> as observed in the rat, for the human situation.</jats:p>\n          </jats:sec>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19767382","pmcid":null,"openalex_id":"https://openalex.org/W4245655569","authors":[],"funders":[],"total_grants":0,"fwci":0.1182,"citation_percentile":0.47798602,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"closed","license":"http://doi.wiley.com/10.1002/tdm_license_1.1","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fhep.510260531","host_type":"publisher"},{"url":"https://journals.lww.com/01515467-199711000-00032","host_type":"publisher"},{"url":"https://doi.org/10.1002/hep.510260531","host_type":"journal"}],"fields_of_study":["RNA Interference and Gene Delivery","Barrier Structure and Function Studies","Neuroinflammation and Neurodegeneration Mechanisms"],"mesh_terms":[],"keywords":["Mannose receptor","Mannose","Receptor","Biochemistry","In vitro","Molecular biology","Chemistry","Biology","Macrophage"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T13:04:49.793776Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}