Acute phase protein, α - 1- acid glycoprotein (AGP-1), has differential effects on TLR-2 and TLR-4 mediated responses.

Autor: Sumanth MS; Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, 570006, Karnataka, India., Abhilasha KV; Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, 570006, Karnataka, India., Jacob SP; Division of Allergy and Immunology, University of Utah, Salt Lake City, UT, 84113, USA., Chaithra VH; Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, 570006, Karnataka, India., Basrur V; Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, MI, USA., Willard B; Research Core Services, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA., McIntyre TM; Department of Cellular & Molecular Medicine, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA., Prabhu KS; Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis, 115 Henning Building, The Pennsylvania State University, University Park, PA, 16802, USA., Marathe GK; Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, 570006, Karnataka, India; Department of Studies in Molecular Biology, University of Mysore, Manasagangothri, Mysuru, 570006, Karnataka, India. Electronic address: marathe1962@gmail.com.
Jazyk: angličtina
Zdroj: Immunobiology [Immunobiology] 2019 Sep; Vol. 224 (5), pp. 672-680. Date of Electronic Publication: 2019 Jun 20.
DOI: 10.1016/j.imbio.2019.06.003
Abstrakt: Alpha-1-acid glycoprotein (AGP-1) is a major positive acute phase glycoprotein with unknown functions that likely play a role in inflammation. We tested its involvement in a variety of inflammatory responses using human AGP-1 purified to apparent homogeneity and confirmed its identity by immunoblotting and mass spectrometry. AGP-1 alone upregulated MAPK signaling in murine peritoneal macrophages. However, when given in combination with TLR ligands, AGP-1 selectively augmented MAPK activation induced by ligands of TLR-2 (Braun lipoprotein) but not TLR-4 (lipopolysaccharide). In vivo treatment of AGP-1 in a murine model of sepsis with or without TLR-2 or TLR-4 ligands, selectively potentiated TLR-2-mediated mortality, but was without significant effect on TLR-4-mediated mortality. Furthermore, in vitro, AGP-1 selectively potentiated TLR-2 mediated adhesion of human primary immune cell, neutrophils. Hence, our studies highlight a new role for the acute phase protein AGP-1 in sepsis via its interaction with TLR-2 signaling mechanisms to selectively promote responsiveness to one of the two major gram-negative endotoxins, contributing to the complicated pathobiology of sepsis.
(Copyright © 2019 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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