Complement C3 and C5 play critical roles in traumatic brain cryoinjury: Blocking effects on neutrophil extravasation by C5a receptor antagonist

Diane L. Sewell, Brendon Nacewicz, Frances Liu, Sinarack Macvilay, A. Erdei, John D. Lambris, Matyas Sandor, Zsuzsa Fabry

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

The role of complement components in traumatic brain injury is poorly understood. Here we show that secondary damage after acute cryoinjury is significantly reduced in C3-/- or C5-/- mice or in mice treated with C5a receptor antagonist peptides. Injury sizes and neutrophil extravasation were compared. While neutrophil density increased following traumatic brain injury in wild type (C57BL/6) mice, C3-deficient mice demonstrated lower neutrophil extravasation and injury sizes in the brain. RNase protection assay indicated that C3 contributes to the induction of brain inflammatory mediators, MIF, RANTES (CCL5) and MCP-1 (CCL2). Intracranial C3 injection induced neutrophil extravasation in injured brains of C3-/- mice suggesting locally produced C3 is important in brain inflammation. We show that neutrophil extravasation is significantly reduced in both C5-/- mice and C5a receptor antagonist treated cryoinjured mice suggesting that one of the possible mechanisms of C3 effect on neutrophil extravasation is mediated via downstream complement activation products such as C5a. Our data indicates that complement inhibitors may ameliorate traumatic brain injury.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalJournal of Neuroimmunology
Volume155
Issue number1-2
DOIs
Publication statusPublished - Oct 2004

Fingerprint

Anaphylatoxin C5a Receptor
Complement C5
Complement C3
Neutrophils
Brain
Complement Inactivating Agents
Chemokine CCL5
Complement Activation
Wounds and Injuries
Encephalitis
Ribonucleases
Inbred C57BL Mouse
Peptides
Injections

Keywords

  • Chemokines
  • CNS
  • Cryoinjury
  • Cytokines
  • Inflammation
  • Neutrophil
  • Trauma

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Complement C3 and C5 play critical roles in traumatic brain cryoinjury : Blocking effects on neutrophil extravasation by C5a receptor antagonist. / Sewell, Diane L.; Nacewicz, Brendon; Liu, Frances; Macvilay, Sinarack; Erdei, A.; Lambris, John D.; Sandor, Matyas; Fabry, Zsuzsa.

In: Journal of Neuroimmunology, Vol. 155, No. 1-2, 10.2004, p. 55-63.

Research output: Contribution to journalArticle

Sewell, Diane L. ; Nacewicz, Brendon ; Liu, Frances ; Macvilay, Sinarack ; Erdei, A. ; Lambris, John D. ; Sandor, Matyas ; Fabry, Zsuzsa. / Complement C3 and C5 play critical roles in traumatic brain cryoinjury : Blocking effects on neutrophil extravasation by C5a receptor antagonist. In: Journal of Neuroimmunology. 2004 ; Vol. 155, No. 1-2. pp. 55-63.
@article{91c34e91c2ab4023b35a93efd19fc7cf,
title = "Complement C3 and C5 play critical roles in traumatic brain cryoinjury: Blocking effects on neutrophil extravasation by C5a receptor antagonist",
abstract = "The role of complement components in traumatic brain injury is poorly understood. Here we show that secondary damage after acute cryoinjury is significantly reduced in C3-/- or C5-/- mice or in mice treated with C5a receptor antagonist peptides. Injury sizes and neutrophil extravasation were compared. While neutrophil density increased following traumatic brain injury in wild type (C57BL/6) mice, C3-deficient mice demonstrated lower neutrophil extravasation and injury sizes in the brain. RNase protection assay indicated that C3 contributes to the induction of brain inflammatory mediators, MIF, RANTES (CCL5) and MCP-1 (CCL2). Intracranial C3 injection induced neutrophil extravasation in injured brains of C3-/- mice suggesting locally produced C3 is important in brain inflammation. We show that neutrophil extravasation is significantly reduced in both C5-/- mice and C5a receptor antagonist treated cryoinjured mice suggesting that one of the possible mechanisms of C3 effect on neutrophil extravasation is mediated via downstream complement activation products such as C5a. Our data indicates that complement inhibitors may ameliorate traumatic brain injury.",
keywords = "Chemokines, CNS, Cryoinjury, Cytokines, Inflammation, Neutrophil, Trauma",
author = "Sewell, {Diane L.} and Brendon Nacewicz and Frances Liu and Sinarack Macvilay and A. Erdei and Lambris, {John D.} and Matyas Sandor and Zsuzsa Fabry",
year = "2004",
month = "10",
doi = "10.1016/j.jneuroim.2004.06.003",
language = "English",
volume = "155",
pages = "55--63",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Complement C3 and C5 play critical roles in traumatic brain cryoinjury

T2 - Blocking effects on neutrophil extravasation by C5a receptor antagonist

AU - Sewell, Diane L.

AU - Nacewicz, Brendon

AU - Liu, Frances

AU - Macvilay, Sinarack

AU - Erdei, A.

AU - Lambris, John D.

AU - Sandor, Matyas

AU - Fabry, Zsuzsa

PY - 2004/10

Y1 - 2004/10

N2 - The role of complement components in traumatic brain injury is poorly understood. Here we show that secondary damage after acute cryoinjury is significantly reduced in C3-/- or C5-/- mice or in mice treated with C5a receptor antagonist peptides. Injury sizes and neutrophil extravasation were compared. While neutrophil density increased following traumatic brain injury in wild type (C57BL/6) mice, C3-deficient mice demonstrated lower neutrophil extravasation and injury sizes in the brain. RNase protection assay indicated that C3 contributes to the induction of brain inflammatory mediators, MIF, RANTES (CCL5) and MCP-1 (CCL2). Intracranial C3 injection induced neutrophil extravasation in injured brains of C3-/- mice suggesting locally produced C3 is important in brain inflammation. We show that neutrophil extravasation is significantly reduced in both C5-/- mice and C5a receptor antagonist treated cryoinjured mice suggesting that one of the possible mechanisms of C3 effect on neutrophil extravasation is mediated via downstream complement activation products such as C5a. Our data indicates that complement inhibitors may ameliorate traumatic brain injury.

AB - The role of complement components in traumatic brain injury is poorly understood. Here we show that secondary damage after acute cryoinjury is significantly reduced in C3-/- or C5-/- mice or in mice treated with C5a receptor antagonist peptides. Injury sizes and neutrophil extravasation were compared. While neutrophil density increased following traumatic brain injury in wild type (C57BL/6) mice, C3-deficient mice demonstrated lower neutrophil extravasation and injury sizes in the brain. RNase protection assay indicated that C3 contributes to the induction of brain inflammatory mediators, MIF, RANTES (CCL5) and MCP-1 (CCL2). Intracranial C3 injection induced neutrophil extravasation in injured brains of C3-/- mice suggesting locally produced C3 is important in brain inflammation. We show that neutrophil extravasation is significantly reduced in both C5-/- mice and C5a receptor antagonist treated cryoinjured mice suggesting that one of the possible mechanisms of C3 effect on neutrophil extravasation is mediated via downstream complement activation products such as C5a. Our data indicates that complement inhibitors may ameliorate traumatic brain injury.

KW - Chemokines

KW - CNS

KW - Cryoinjury

KW - Cytokines

KW - Inflammation

KW - Neutrophil

KW - Trauma

UR - http://www.scopus.com/inward/record.url?scp=4444242782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444242782&partnerID=8YFLogxK

U2 - 10.1016/j.jneuroim.2004.06.003

DO - 10.1016/j.jneuroim.2004.06.003

M3 - Article

C2 - 15342196

AN - SCOPUS:4444242782

VL - 155

SP - 55

EP - 63

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 1-2

ER -