Different glycoforms of alpha-1-acid glycoprotein contribute to its functional alterations in platelets and neutrophils.

Autor: Sumanth MS; Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, Karnataka, India., Jacob SP; Department of Pediatrics, Division of Allergy and Immunology, University of Utah, Salt Lake City, Utah, USA., Abhilasha KV; Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, Karnataka, India., Manne BK; Molecular Medicine Program, and Department of Internal Medicine and Pathology, University of Utah, Salt Lake City, Utah, USA., Basrur V; Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Lehoux S; Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA., Campbell RA; Molecular Medicine Program, and Department of Internal Medicine and Pathology, University of Utah, Salt Lake City, Utah, USA., Yost CC; Molecular Medicine Program, and Department of Internal Medicine and Pathology, University of Utah, Salt Lake City, Utah, USA.; Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA., McIntyre TM; Department of Cardiovascular & Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA., Cummings RD; Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA., Weyrich AS; Molecular Medicine Program, and Department of Internal Medicine and Pathology, University of Utah, Salt Lake City, Utah, USA., Rondina MT; Molecular Medicine Program, and Department of Internal Medicine and Pathology, University of Utah, Salt Lake City, Utah, USA.; The Geriatric Research Education and Clinical Center, Salt Lake City, Utah, USA.; Department of Internal Medicine, George E. Wahlen VAMC, Salt Lake City, Utah, USA., Marathe GK; Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, Karnataka, India.; Department of Studies in Molecular Biology, University of Mysore, Manasagangothri, Mysuru, Karnataka, India.
Jazyk: angličtina
Zdroj: Journal of leukocyte biology [J Leukoc Biol] 2021 May; Vol. 109 (5), pp. 915-930. Date of Electronic Publication: 2020 Oct 18.
DOI: 10.1002/JLB.3A0720-422R
Abstrakt: 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 12-20 different glycoforms. We isolated a glycoform secreted from platelet-activating factor (PAF)-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 behavior, electrophoretic mobility, and pattern of glycosylation. The function of these 2 glycoforms also differed. sAGP-1 activated neutrophil adhesion, migration, and neutrophil extracellular traps (NETosis) involving myeloperoxidase, peptidylarginine deiminase 4, and phosphorylation of ERK in a dose-dependent fashion, whereas nAGP-1 was ineffective as an agonist for these events. Furthermore, sAGP-1, but not nAGP-1, inhibited LPS-stimulated NETosis. Interestingly, 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 PAF or ADP, but not by thrombin. These functional effects of sAGP-1 correlated with intracellular cAMP accumulation and phosphorylation of the protein kinase A substrate vasodilator-stimulated phosphoprotein and reduction of Akt, ERK, and p38 phosphorylation. Thus, the sAGP-1 glycoform limits platelet reactivity, whereas nAGP-1 glycoform also limits proinflammatory 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 2 critical cells of acute inflammation.
(©2020 Society for Leukocyte Biology.)
Databáze: MEDLINE
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