High-mobility group box 1-induced complement activation causes sterile inflammation

Sook Young Kim, Myoungsun Son, Sang Eun Lee, In Ho Park, Man Sup Kwak, Myeonggil Han, Hyun Sook Lee, Eun Sook Kim, Jae Young Kim, Jongeun Lee, Ji Eun Choi, Betty Diamond, Jeon Soo Shin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q. The C3a complement activation product in human plasma and C5b-9 membrane attack complexes on cell membrane surface are detected after the addition of HMGB1. In an acetaminophen (APAP)-induced hepatotoxicity model, APAP injection reduced HMGB1 levels and elevated C3 levels in C1q-deficient mouse serum samples, compared to that in wild-type (WT) mice. APAP-induced C3 consumption was inhibited by sRAGE treatment in WT mice. Moreover, in a mouse model of brain ischemia-reperfusion injury based on middle cerebral arterial occlusion, C5b-9 complexes were deposited on vessels where HMGB1 was accumulated, an effect that was suppressed upon HMGB1 neutralization. We propose that the HMGB1 released after cell necrosis and in ischemic condition can trigger the classical pathway of complement activation to exacerbate sterile inflammation.

Original languageEnglish
Article number705
JournalFrontiers in Immunology
Volume9
Issue numberAPR
DOIs
Publication statusPublished - 2018 Apr 11

Fingerprint

Complement Activation
Acetaminophen
Complement Membrane Attack Complex
Classical Complement Pathway
Inflammation
Reperfusion Injury
Brain Ischemia
Necrosis
Cell Membrane
Injections
Antibodies
Serum
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kim, S. Y., Son, M., Lee, S. E., Park, I. H., Kwak, M. S., Han, M., ... Shin, J. S. (2018). High-mobility group box 1-induced complement activation causes sterile inflammation. Frontiers in Immunology, 9(APR), [705]. https://doi.org/10.3389/fimmu.2018.00705
Kim, Sook Young ; Son, Myoungsun ; Lee, Sang Eun ; Park, In Ho ; Kwak, Man Sup ; Han, Myeonggil ; Lee, Hyun Sook ; Kim, Eun Sook ; Kim, Jae Young ; Lee, Jongeun ; Choi, Ji Eun ; Diamond, Betty ; Shin, Jeon Soo. / High-mobility group box 1-induced complement activation causes sterile inflammation. In: Frontiers in Immunology. 2018 ; Vol. 9, No. APR.
@article{1d4e52818ded4d7bbdf48ddc7ad5972f,
title = "High-mobility group box 1-induced complement activation causes sterile inflammation",
abstract = "High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q. The C3a complement activation product in human plasma and C5b-9 membrane attack complexes on cell membrane surface are detected after the addition of HMGB1. In an acetaminophen (APAP)-induced hepatotoxicity model, APAP injection reduced HMGB1 levels and elevated C3 levels in C1q-deficient mouse serum samples, compared to that in wild-type (WT) mice. APAP-induced C3 consumption was inhibited by sRAGE treatment in WT mice. Moreover, in a mouse model of brain ischemia-reperfusion injury based on middle cerebral arterial occlusion, C5b-9 complexes were deposited on vessels where HMGB1 was accumulated, an effect that was suppressed upon HMGB1 neutralization. We propose that the HMGB1 released after cell necrosis and in ischemic condition can trigger the classical pathway of complement activation to exacerbate sterile inflammation.",
author = "Kim, {Sook Young} and Myoungsun Son and Lee, {Sang Eun} and Park, {In Ho} and Kwak, {Man Sup} and Myeonggil Han and Lee, {Hyun Sook} and Kim, {Eun Sook} and Kim, {Jae Young} and Jongeun Lee and Choi, {Ji Eun} and Betty Diamond and Shin, {Jeon Soo}",
year = "2018",
month = "4",
day = "11",
doi = "10.3389/fimmu.2018.00705",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "APR",

}

Kim, SY, Son, M, Lee, SE, Park, IH, Kwak, MS, Han, M, Lee, HS, Kim, ES, Kim, JY, Lee, J, Choi, JE, Diamond, B & Shin, JS 2018, 'High-mobility group box 1-induced complement activation causes sterile inflammation', Frontiers in Immunology, vol. 9, no. APR, 705. https://doi.org/10.3389/fimmu.2018.00705

High-mobility group box 1-induced complement activation causes sterile inflammation. / Kim, Sook Young; Son, Myoungsun; Lee, Sang Eun; Park, In Ho; Kwak, Man Sup; Han, Myeonggil; Lee, Hyun Sook; Kim, Eun Sook; Kim, Jae Young; Lee, Jongeun; Choi, Ji Eun; Diamond, Betty; Shin, Jeon Soo.

In: Frontiers in Immunology, Vol. 9, No. APR, 705, 11.04.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - High-mobility group box 1-induced complement activation causes sterile inflammation

AU - Kim, Sook Young

AU - Son, Myoungsun

AU - Lee, Sang Eun

AU - Park, In Ho

AU - Kwak, Man Sup

AU - Han, Myeonggil

AU - Lee, Hyun Sook

AU - Kim, Eun Sook

AU - Kim, Jae Young

AU - Lee, Jongeun

AU - Choi, Ji Eun

AU - Diamond, Betty

AU - Shin, Jeon Soo

PY - 2018/4/11

Y1 - 2018/4/11

N2 - High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q. The C3a complement activation product in human plasma and C5b-9 membrane attack complexes on cell membrane surface are detected after the addition of HMGB1. In an acetaminophen (APAP)-induced hepatotoxicity model, APAP injection reduced HMGB1 levels and elevated C3 levels in C1q-deficient mouse serum samples, compared to that in wild-type (WT) mice. APAP-induced C3 consumption was inhibited by sRAGE treatment in WT mice. Moreover, in a mouse model of brain ischemia-reperfusion injury based on middle cerebral arterial occlusion, C5b-9 complexes were deposited on vessels where HMGB1 was accumulated, an effect that was suppressed upon HMGB1 neutralization. We propose that the HMGB1 released after cell necrosis and in ischemic condition can trigger the classical pathway of complement activation to exacerbate sterile inflammation.

AB - High-mobility group box 1 (HMGB1), a well-known danger-associated molecular pattern molecule, acts as a pro-inflammatory molecule when secreted by activated immune cells or released after necrotic cell damage. HMGB1 binds to immunogenic bacterial components and augments septic inflammation. In this study, we show how HMGB1 mediates complement activation, promoting sterile inflammation. We show that HMGB1 activates the classical pathway of complement system in an antibody-independent manner after binding to C1q. The C3a complement activation product in human plasma and C5b-9 membrane attack complexes on cell membrane surface are detected after the addition of HMGB1. In an acetaminophen (APAP)-induced hepatotoxicity model, APAP injection reduced HMGB1 levels and elevated C3 levels in C1q-deficient mouse serum samples, compared to that in wild-type (WT) mice. APAP-induced C3 consumption was inhibited by sRAGE treatment in WT mice. Moreover, in a mouse model of brain ischemia-reperfusion injury based on middle cerebral arterial occlusion, C5b-9 complexes were deposited on vessels where HMGB1 was accumulated, an effect that was suppressed upon HMGB1 neutralization. We propose that the HMGB1 released after cell necrosis and in ischemic condition can trigger the classical pathway of complement activation to exacerbate sterile inflammation.

UR - http://www.scopus.com/inward/record.url?scp=85045232662&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045232662&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2018.00705

DO - 10.3389/fimmu.2018.00705

M3 - Article

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - APR

M1 - 705

ER -