Does activation of the FcgammaRIIa play a role in the pathogenesis of the acute lung injury/acute respiratory distress syndrome?
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 FcgammaRIIa (Fcgamma IIa receptor) in lungs of patients with ARDS. Furthermore, the expression of FcgammaRIIa is substantially elevated in lungs of these patients. FcgammaRIIa 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. FcgammaRs 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 FcgammaRs are essential for these complexes to cause damage to the lungs. Therefore, we hypothesize that FcgammaRs such as FcgammaRIIa could contribute to the pathogenesis of ALI/ARDS.
Fudala
Rafal
R
Department of Biochemistry, University of Texas Health Science Center, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Krupa
Agnieszka
A
Stankowska
Dorota
D
Allen
Timothy C
TC
Kurdowska
Anna K
AK
D055371:Acute Lung Injury / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis; D004195:Disease Models, Animal; D019317:Evidence-Based Medicine; D006801:Humans; D008024:Ligands; D008168:Lung / Q000276:immunology; D051379:Mice; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D012128:Respiratory Distress Syndrome / Q000235:genetics / Q000276:immunology* / Q000628:therapy
D000936:Antigen-Antibody Complex; C080568:Fc gamma receptor IIA; D008024:Ligands; D017452:Receptors, IgG