Cell surface expression of HFE protein in epithelial cells, macrophages, and monocytes

Background and Objectives. Most patients with hereditary hemochromatosis ar e homozygous for a Cys282 --> Tyr mutation In the HFE gene. This mutation h as been shown to impair the association of the HFE gene product with beta(2 )-microglobulin and to prevent its cell surface presentation in transfected COS-7 and 293 cells. This study was performed to line the expression of HF E protein in epithelial macrophages, and circulating leukocytes obtained fr om normal subjects and patients with hereditary hemochromatosis, Design and Methods. Antisera against two different peptides of the HFE prot ein were used to immunostain tissue sections and isolate granulocytes, lymp hocytes and monocytes. Results. Immunocytochemical staining showed that HFE protein Is expressed i n gastric epithelial cells, tissue macrophages, and circulating monocytes a nd granulocytes, The cell surface associated signal, which was seen in norm al gastric epithelial cells, monocytes and macrophages, was also present in C282Y mutant cells from patients with hereditary hemochromatosis, although at apparently reduced amounts in these cells. Interpretation and Conclusions. From these studies, It is clear that the C2 82Y mutation reduces but does not completely prevent presentation of the HF E protein on the cell surface of human monocytes, tissue macrophages, and g astric epithelial cells. (C) 2000, Ferrata Storti Foundation.