{"doi":"10.1371/journal.pone.0250327","title":"High molecular weight sodium hyaluronate improves survival of syndecan-1-deficient septic mice by inhibiting neutrophil migration","abstract":"METHODS: Sepsis was induced by cotton smoke inhalation followed by intranasal administration of Pseudomonas aeruginosa in female (> 6 months) Balb/c and syndecan-1 knockout mice. Survival of mice, lung capillary endothelial glycocalyx integrity, lung water content, and vascular hyper-permeability were determined with or without HMW-SH treatment in these mice. Effects of HMW-SH on endothelial permeability and neutrophil migration were tested in in vitro setting. RESULTS: In septic wildtype mice, we found a severely damaged pulmonary microvascular endothelial glycocalyx and elevated levels of shed syndecan-1 in the circulation. These changes were associated with significantly increased pulmonary vascular permeability. In septic syndecan-1 knockout mice, extravascular lung water content was higher, and early death was observed. The administration of HMW-SH significantly reduced mortality and lung water content in septic syndecan-1 knockout mice, but not in septic wildtype mice. In in vitro setting, HMW-SH inhibited neutrophil migration and reduced cultured endothelial cell permeability increases. However, these effects were reversed by the addition of recombinant syndecan-1 ectodomain. CONCLUSIONS: HMW-SH reduced lung tissue damage and mortality in the absence of syndecan-1 protein, possibly by reducing vascular hyper-permeability and neutrophil migration. Our results further suggest that increased shed syndecan-1 protein levels are linked with the inefficiency of HMW-SH in septic wildtype mice.","journal":"PLoS ONE","year":2021,"id":185667,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":441714,"name":"Enkhtuya Radnaa","orcid":"0000-0001-8142-8137","position":1,"is_corresponding":false},{"id":742869,"name":"Casey M. Ouellette","orcid":null,"position":2,"is_corresponding":false},{"id":742299,"name":"Christina Nelson","orcid":"0009-0004-9350-5952","position":3,"is_corresponding":false},{"id":442136,"name":"Yosuke Niimi","orcid":"0000-0002-4203-380X","position":4,"is_corresponding":false},{"id":442137,"name":"Clark R. Andersen","orcid":"0000-0003-1846-9117","position":5,"is_corresponding":false},{"id":275506,"name":"Vsevolod L. Popov","orcid":"0000-0001-6155-7150","position":6,"is_corresponding":false},{"id":451913,"name":"Jae Woo Lee","orcid":"0000-0002-6521-8647","position":7,"is_corresponding":false},{"id":442138,"name":"Donald S. Prough","orcid":"0000-0001-7994-532X","position":8,"is_corresponding":false},{"id":442139,"name":"Perenlei Enkhbaatar","orcid":"0000-0002-0545-2028","position":9,"is_corresponding":false},{"id":742298,"name":"Tuvshintugs Baljinnyam","orcid":"0000-0001-8664-9318","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:48:38.805613Z","pmid":"33930030","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":[]}