Anti-KC autoantibody:KC complexes cause severe lung inflammation in mice via IgG receptors.
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 (FcgammaRs) 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-functional IL-8) in lungs of mice to develop a mouse model of autoimmune complex-induced lung inflammation. Both wild-type (WT) and gamma-chain-deficient mice that lack receptors for immune complexes (FcgammaRs) 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 gamma-chain-deficient mice. Second, because sepsis is considered the major risk factor for development of ARDS, we evaluated LPS-treated WT as well as gamma-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, gamma-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.
Krupa
Agnieszka
A
Department of Biochemistry, University of Texas Health Center, Tyler, Texas 75708-3154, USA.
Walencka
Maria J
MJ
Shrivastava
Vivek
V
Loyd
Tameka
T
Fudala
Rafal
R
Frevert
Charles W
CW
Martin
Thomas R
TR
Kurdowska
Anna K
AK
D000818:Animals; D000936:Antigen-Antibody Complex / Q000009:adverse effects*; D001323:Autoantibodies / Q000009:adverse effects*; D054360:Chemokine CXCL1 / Q000276:immunology*; D004195:Disease Models, Animal; D007105:Immune Complex Diseases / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology*; D017452:Receptors, IgG / Q000502:physiology*; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000473:pathology; D012720:Severity of Illness Index
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D017452:Receptors, IgG