{"doi":"10.1101/2020.02.27.968974","title":"Differential glycosylation of alpha-1-acid glycoprotein (AGP-1) contributes to its functional diversity","abstract":"Abstract Alpha-1-acid glycoprotein (AGP-1) is a positive acute phase glycoprotein with uncertain functions. Serum AGP-1 (sAGP-1) is primarily derived from hepatocytes and circulates as 12 to 20 different glycoforms. We isolated a glycoform secreted from stimulated human neutrophils (nAGP-1). Its peptide sequence was identical to hepatocyte-derived sAGP-1, but nAGP-1 differed from sAGP-1 in its chromatographic behaviour, electrophoretic mobility, and glycosylation. The function of these two glycoforms also differed. sAGP-1 activated neutrophil adhesion, migration and NETosis in a dose-dependent fashion, while nAGP-1 was ineffective as an agonist for these events. Furthermore, sAGP-1, but not nAGP-1, inhibited LPS-stimulated NETosis. However, nAGP-1 inhibited sAGP-1-stimulated neutrophil NETosis. The discordant effect of the differentially glycosylated AGP-1 glycoforms was also observed in platelets where neither of the AGP-1 glycoforms alone stimulated aggregation of washed human platelets, but sAGP-1, and not nAGP-1, inhibited aggregation induced by Platelet-activating Factor (PAF) or ADP, but not by thrombin. These functional effects of sAGP-1 correlated with intracellular cAMP accumulation and were accompanied by phosphorylation of the PKA substrate Vasodialator stimulated phosphoprotein (VASP) and reduction of Akt, ERK, and p38 phosphorylation. Thus, the sAGP-1 glycoform limits platelet reactivity while nAGP-1 glycoform also limits pro-inflammatory actions of sAGP-1. These studies identify new functions for this acute phase glycoprotein and demonstrate that the glycosylation of AGP-1 controls its effects on two critical cells of acute inflammation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124671,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9624,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":570460,"name":"Shancy Jacob","orcid":null,"position":1,"is_corresponding":false},{"id":432436,"name":"Kandahalli Venkataranganayaka Abhilasha","orcid":"0000-0001-8762-3873","position":2,"is_corresponding":false},{"id":105732,"name":"Bhanu Kanth Manne","orcid":"0000-0001-6848-4484","position":3,"is_corresponding":false},{"id":253569,"name":"Venkatesha Basrur","orcid":"0000-0002-0853-9655","position":4,"is_corresponding":false},{"id":266359,"name":"Sylvain Lehoux","orcid":"0000-0001-6783-5625","position":5,"is_corresponding":false},{"id":105727,"name":"Robert A. Campbell","orcid":"0000-0003-0027-694X","position":6,"is_corresponding":false},{"id":105742,"name":"Christian C. Yost","orcid":"0000-0002-1258-3595","position":7,"is_corresponding":false},{"id":570461,"name":"Matthew T Rhondina","orcid":null,"position":8,"is_corresponding":false},{"id":344668,"name":"Thomas M. McIntyre","orcid":"0000-0001-7802-5900","position":9,"is_corresponding":false},{"id":231529,"name":"Richard D. Cummings","orcid":"0000-0002-8918-5034","position":10,"is_corresponding":false},{"id":105740,"name":"Andrew S. Weyrich","orcid":"0000-0001-9622-4647","position":11,"is_corresponding":false},{"id":569819,"name":"Gopal K. Marathe","orcid":"0000-0002-0025-6677","position":12,"is_corresponding":false},{"id":569818,"name":"Mosale Seetharam Sumanth","orcid":"0000-0003-3557-8198","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:15:11.632153Z","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":[]}