Anti-KC autoantibody:KC complexes cause severe lung inflammation in mice via IgG receptors

Agnieszka Krupa, Maria J. Walencka, Vivek Shrivastava, Tameka Loyd, Rafal Fudala, Charles W. Frevert, Thomas R. Martin, Anna K. Kurdowska

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

We have shown previously that high concentrations of IL-8 associated with anti-IL-8 autoantibodies (anti-IL-8:IL-8 complexes) are present in lung fluids from patients with the acute respiratory distress syndrome (ARDS), and correlate both with the development and outcome of ARDS. We also detected deposition of these complexes in lung tissues from patients with ARDS but not in control tissues. Moreover, we determined that IgG receptors (FCγRS) mediate activity of anti-IL-8:IL-8 complexes. In the current study, we generated anti-KC (KC = chemokine (CXC motif) ligand 1 (CXCL1)) autoantibody:KC immune complexes (KC-f unctional IL-8) in lungs of mice to develop a mouse model of autoimmune complex-induced lung inflammation. Both wild-type (WT) and γ-chain- deficient mice that lack receptors for immune complexes (FcγRs) were studied. First, the mice were immunized with KC to induce anti-KC autoantibodies. Then, KC was administered intratracheally to generate anti-KC:KC complexes in the lung. Presence of anti-KC:KC complexes was associated with development of severe pulmonary inflammation that was, however, dramatically suppressed in γ-chain-deficient mice. Second, because sepsis is considered the major risk factor for development of ARDS, we evaluated LPS-treated WT as well as γ-chain-deficient mice for the presence of anti-KC:KC complexes and pulmonary inflammatory responses. We detected complexes between anti-KC autoantibodies and KC in lung lavages and tissues of mice treated with LPS. Moreover, γ-chain-deficient mice that lack receptors for immune complexes were protected from LPS-induced pulmonary inflammation. Our results suggest that immune complexes containing autoantibodies contribute to development of lung inflammation in LPS-treated mice.

Original languageEnglish
Pages (from-to)532-543
Number of pages12
JournalAmerican journal of respiratory cell and molecular biology
Volume37
Issue number5
DOIs
StatePublished - Nov 2007

Keywords

  • Autoantibody
  • Chemokine
  • Endotoxin
  • Immune complex
  • Lung

Fingerprint Dive into the research topics of 'Anti-KC autoantibody:KC complexes cause severe lung inflammation in mice via IgG receptors'. Together they form a unique fingerprint.

  • Cite this