Anti-chemokine autoantibody: Chemokine immune complexes activate endothelial cells via IgG receptors

Agnieszka Krupa, Rafal Fudala, Dorota Stankowska, Tameka Loyd, Timothy C. Allen, Michael A. Matthay, Zygmunt Gryczynski, Ignacy Gryczynski, Yalla V. Mettikolla, Anna K. Kurdowska

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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, FcγRIIa. Importantly, increased levels of FcγRIIa are present inlungs of patients with ARDS, where FcγRIIa 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 FcγRIIa. 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-κB. 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 γ 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.

Original languageEnglish (US)
Pages (from-to)155-169
Number of pages15
JournalAmerican journal of respiratory cell and molecular biology
Volume41
Issue number2
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

Keywords

  • Autoantibody
  • Chemokine
  • IgG receptor
  • Lung

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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