Conjugation was performed using succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate. Polyclonal antibodies specific for a peptide corresponding to the carboxyterminus of sH2a or to a peptide unique to sH2a (169 antibody) were described in earlier studies.Ī monoclonal antibody was prepared by intraperitoneal immunization of BALB/c mice with a conjugate of keyhole limpet hemocyanin (KLH) with the carboxyterminal peptide of H2 and complete Freunds adjuvant. Here we show for a group of healthy individuals that ASGPR sH2a is secreted to the serum at surprisingly constant levels, and that these are much reduced in hepatitis C virus (HCV) patients with liver cirrhosis. SH2a is formed by cleavage in the endoplasmic reticulum of its precursor, encoded by an alternatively spliced variant of the ASGPR H2 subunit mRNA, and does not arise by shedding at the cell surface. We had previously described a soluble form of the ASGPR, termed sH2a, secreted from the human hepatoma cell line HepG2. The levels of the ASGPR are much reduced upon hepatocyte dedifferentiation, upon chronic alcohol consumption and in liver fibrosis and cirrhosis. As evaluated through whole-body scintigraphy, using a radioactive ASGPR ligand, a technetium-99m-labeled asialoglycoprotein analog, only the liver shows any significant expression of the ASGPR. The human asialoglycoprotein receptor (ASGPR) is expressed on the sinusoidal membrane of hepatocytes and serves in the clearance of asialoglycoproteins from the plasma.