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, Anna Erdei, John D. Lambris, Matyas Sandor, Zsuzsa Fabry

Research output: Contribution to journalArticle

97 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 1 2004

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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