Expression, saturation, and endocytosis of
IgA Fc receptors (Fc alpha R) were analyzed in blood phagocytic cells of patients with
alcoholic liver cirrhosis (ALC). Surface Fc alpha R expression was decreased in monocytes but not in neutrophils, as evaluated by
IgA binding and anti-Fc alpha R mAb. The Fc alpha R of ALC patients were saturated by
IgA1 and
IgA2. ALC Fc alpha R had a higher M(r) (60 to 90 kDa) than those of controls (55 to 75 kDa) with a similar 32-kDa
protein core after
N-glycanase treatment, suggesting the expression of Fc alpha R molecules with altered
carbohydrate moieties. Treatment of U937 cells with IFN-gamma induced a decrease of surface Fc alpha R expression in a dose-dependent manner, with a similar M(r) as observed for ALC patient Fc alpha R (60 to 90 kDa). Fc alpha R endocytosis was induced by anti-Fc alpha R or
IgA. Neutrophils internalized Fc alpha R molecules faster than did monocytes. Endocytosed Fc alpha R co-localized with
cathepsin D, suggesting an endolysosomal compartment pathway. In ALC monocytes, Fc alpha R endocytosis was defective, with nearly 50 to 60% of receptors detected on the cell surface even after 90 min at 37 degrees C. Similarly, delayed Fc alpha R endocytosis was observed on IFN-gamma-treated U937 cells as compared with PMA-activated cells. Defective internalization of surface-bound
IgA with reflux of
IgA to cell surface was also observed on ALC monocytes, but not on normal cells preincubated with patients' plasma, ruling out direct effects of
IgA. The inverse correlation between monocyte Fc alpha R levels and serum
IgA levels associated with defective endocytosis suggest that altered Fc alpha R expression might contribute to receptor saturation and generation of increased plasma levels of
IgA and
IgA-
immune complexes in ALC patients.