title: Anti-chemokine autoantibody:chemokine immune complexes activate endothelial cells via IgG receptors.
abstract: Our previous studies revealed that the presence in lung fluids of anti-IL-8 autoantibody:IL-8 immune complexes is an important prognostic indicator for the development and outcome of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Anti-IL-8:IL-8 complexes purified from lung edema fluids trigger chemotaxis of neutrophils, induce activation of these cells, and regulate their apoptosis, all via IgG receptor, FcgammaRIIa. Importantly, increased levels of FcgammaRIIa are present in lungs of patients with ARDS, where FcgammaRIIa is partially associated with anti-IL-8:IL-8 complexes. In the current study, we demonstrate the ability of anti-IL-8:IL-8 complexes to promote an inflammatory phenotype of human umbilical vein endothelial cells via interaction with FcgammaRIIa. Human umbilical vein endothelial cells cultured in the presence of the complexes become activated, as shown by increased phosphorylation of ERK, JNK, and Akt, and augmented nuclear translocation of NF-kappaB. Anti-IL-8:IL-8 complexes also up-regulate expression of intracellular adhesion molecule (ICAM)-1 on the cell surface. Furthermore, we detected increased levels of ICAM-1 on lung endothelial cells from mice in which lung injury was induced by generating immune complexes in alveolar spaces. On the other hand, ICAM-1 expression was unchanged in lungs of gamma chain-deficient mice, lacking receptors that interact with immune complexes. Moreover, in lung tissues from patients with ARDS, anti-IL-8:IL-8 complexes were associated with endothelial cells that expressed higher levels of ICAM-1. Our current findings implicate that anti-chemokine autoantibody:chemokine immune complexes, such as IL-8:IL-8 complexes, may contribute to pathogenesis of lung inflammation by inducing activation of endothelial cells through engagement of IgG receptors.
authors.affiliation: Department of Biochemistry, University of Texas Health Center, 11,937 U.S. Highway 271, Tyler, Texas 75708-3154, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Krupa
authors.forename: Rafal
authors.initials: R
authors.lastname: Fudala
authors.forename: Dorota
authors.initials: D
authors.lastname: Stankowska
authors.forename: Tameka
authors.initials: T
authors.lastname: Loyd
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Allen
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Gryczynski
authors.forename: Ignacy
authors.initials: I
authors.lastname: Gryczynski
authors.forename: Yalla V
authors.initials: YV
authors.lastname: Mettikolla
authors.forename: Anna K
authors.initials: AK
authors.lastname: Kurdowska
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D018952:Antigens, CD34 / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D018952:Antigens, CD34; D001323:Autoantibodies; C080568:Fc gamma receptor IIA; D016209:Interleukin-8; D017452:Receptors, IgG; D051996:Transcription Factor RelA; D018799:Intercellular Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases