Does activation of the Fcγ RIIa play a role in the pathogenesis of the acute lung injury/acute respiratory distress syndrome?

Rafal Fudala, Agnieszka Krupa, Dorota Stankowska, Timothy C. Allen, Anna K. Kurdowska

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

ALI (acute lung injury) and its more severe form ARDS (acute respiratory distress syndrome) are inflammatory diseases of the lung characterized by hypoxaemia and diffuse bilateral infiltrates. Disruption of epithelial integrity and injury to endothelium are contributing factors of the development of ALI/ARDS, and alveolar damage is the most pronounced feature of ALI/ARDS. The resulting increase in lung microvascular permeability promotes influx of inflammatory cells to the alveolar spaces. Oedema fluid contains pro-nflammatory mediators and plasma proteins, including Igs (immunoglobulins). Moreover, several reports describe the presence of autoantibodies and immune complexes [anti-IL-8 (interleukin-8) autoantibody/IL-8 complexes] in lung fluids (oedema and bronchoalveolar lavage fluids) from patients with ALI/ARDS. These immune complexes associate with FcγRIIa (Fcγ IIa receptor) in lungs of patients with ARDS. Furthermore, the expression of Fcγ RIIa is substantially elevated in lungs of these patients. Fcγ RIIa appears on virtually all myeloid cells, platelets and endothelial cells. It is a low-affinity receptor for IgG that preferentially binds aggregated immunoglobulins and immune complexes. Fcγ Rs regulate phagocytosis and cell-mediated cytotoxicity, and initiate the release of inflammatory mediators. It should be noted that immune complexes formed between either anti-neutrophil autoantibodies and their specific antigens or anti-HLA (human leucocyte antigen) antibodies and target antigens are implicated in the pathogenesis of TRALI (transfusion-related acute lung injury), and importantly, animal studies indicate that FcγRs are essential for these complexes to cause damage to the lungs. Therefore, we hypothesize that FcγRs such as FcγRIIa could contribute to the pathogenesis of ALI/ARDS.

Original languageEnglish
Pages (from-to)519-526
Number of pages8
JournalClinical Science
Volume118
Issue number8
DOIs
StatePublished - 23 Feb 2010

Keywords

  • Acute lung injury
  • Fcγ RIIa
  • IgG receptor
  • Lung
  • Signal transduction

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