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

Mosale Seetharam Sumanth, Kandahalli Venkataranganayaka Abhilasha, Shancy Petsel Jacob, Vyala Hanumanthareddy Chaithra, Venkatesha Basrur, Belinda Willard, Thomas M. McIntyre, K. Sandeep Prabhu, Gopal K. Marathe

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)672-680
Number of pages9
JournalImmunobiology
Volume224
Issue number5
DOIs
StatePublished - Sep 2019

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Acute-Phase Proteins
Sepsis
Glycoproteins
Ligands
Acids
Orosomucoid
Mortality
Peritoneal Macrophages
Immunoblotting
Endotoxins
Lipoproteins
Lipopolysaccharides
Mass Spectrometry
Neutrophils
Inflammation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Hematology

Cite this

Sumanth, M. S., Abhilasha, K. V., Jacob, S. P., Chaithra, V. H., Basrur, V., Willard, B., ... Marathe, G. K. (2019). Acute phase protein, α – 1- acid glycoprotein (AGP-1), has differential effects on TLR-2 and TLR-4 mediated responses. Immunobiology, 224(5), 672-680. https://doi.org/10.1016/j.imbio.2019.06.003
Sumanth, Mosale Seetharam ; Abhilasha, Kandahalli Venkataranganayaka ; Jacob, Shancy Petsel ; Chaithra, Vyala Hanumanthareddy ; Basrur, Venkatesha ; Willard, Belinda ; McIntyre, Thomas M. ; Prabhu, K. Sandeep ; Marathe, Gopal K. / Acute phase protein, α – 1- acid glycoprotein (AGP-1), has differential effects on TLR-2 and TLR-4 mediated responses. In: Immunobiology. 2019 ; Vol. 224, No. 5. pp. 672-680.
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abstract = "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.",
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Sumanth, MS, Abhilasha, KV, Jacob, SP, Chaithra, VH, Basrur, V, Willard, B, McIntyre, TM, Prabhu, KS & Marathe, GK 2019, 'Acute phase protein, α – 1- acid glycoprotein (AGP-1), has differential effects on TLR-2 and TLR-4 mediated responses', Immunobiology, vol. 224, no. 5, pp. 672-680. https://doi.org/10.1016/j.imbio.2019.06.003

Acute phase protein, α – 1- acid glycoprotein (AGP-1), has differential effects on TLR-2 and TLR-4 mediated responses. / Sumanth, Mosale Seetharam; Abhilasha, Kandahalli Venkataranganayaka; Jacob, Shancy Petsel; Chaithra, Vyala Hanumanthareddy; Basrur, Venkatesha; Willard, Belinda; McIntyre, Thomas M.; Prabhu, K. Sandeep; Marathe, Gopal K.

In: Immunobiology, Vol. 224, No. 5, 09.2019, p. 672-680.

Research output: Contribution to journalArticle

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T1 - Acute phase protein, α – 1- acid glycoprotein (AGP-1), has differential effects on TLR-2 and TLR-4 mediated responses

AU - Sumanth, Mosale Seetharam

AU - Abhilasha, Kandahalli Venkataranganayaka

AU - Jacob, Shancy Petsel

AU - Chaithra, Vyala Hanumanthareddy

AU - Basrur, Venkatesha

AU - Willard, Belinda

AU - McIntyre, Thomas M.

AU - Prabhu, K. Sandeep

AU - Marathe, Gopal K.

PY - 2019/9

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N2 - 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.

AB - 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.

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