ASGR1 and ASGR2, the Genes that Encode the Asialoglycoprotein Receptor (Ashwell Receptor), Are Expressed in Peripheral Blood Monocytes and Show Interindividual Differences in Transcript Profile
Background. The asialoglycoprotein receptor (ASGPR) is a hepatic receptor that mediates removal of potentially hazardous glycoconjugates from blood in health and disease. The receptor comprises two proteins, asialoglycoprotein receptor 1 and 2 (ASGR1 and ASGR2), encoded by the genes ASGR1 and ASGR2. Design and Methods. Using reverse transcription amplification (RT-PCR), expression of ASGR1 and ASGR2 was investigated in human peripheral blood monocytes. Results. Monocytes were found to express ASGR1 and ASGR2 transcripts. Correctly spliced transcript variants encoding different isoforms of ASGR1 and ASGR2 were present in monocytes. The profile of transcript variants from both ASGR1 and ASGR2 differed among individuals. Transcript expression levels were compared with the hepatocyte cell line HepG2 which produces high levels of ASGPR. Monocyte transcripts were 4 to 6 orders of magnitude less than in HepG2 but nonetheless readily detectable using standard RT-PCR. The monocyte cell line THP1 gave similar results to monocytes harvested from peripheral blood, indicating it may provide a suitable model system for studying ASGPR function in this cell type. Conclusions. Monocytes transcribe and correctly process transcripts encoding the constituent proteins of the ASGPR. Monocytes may therefore represent a mobile pool of the receptor, capable of reaching sites remote from the liver. 1. Introduction The asialoglycoprotein receptor (ASGPR) (also known as the Ashwell receptor) mediates the capture and endocytosis of galactose- (Gal) and N-acetylgalactosamine- (GalNAc) terminating glycoproteins. The relevance of this function has been the subject of much debate; the primary role may be the removal of potentially hazardous glycoconjugates arising from normal tissue turnover, tissue injury, disease, and other causes [1]. Studies using knock-out mice have provided evidence for direct involvement of the ASGPR in removal of abnormally sialylated plasma glycoproteins. Mice lacking the sialyltransferase ST3Gal4 showed prolonged bleeding which was attributed to ASGPR-mediated clearance of at least one plasma hemostatic component, von Willebrand factor (VWF), that showed decreased sialylation [2]. Findings in mice lacking the ASGPR demonstrated that, during sepsis, the receptor removed components of hemostasis (VWF and platelets) that had been desialylated by bacterial neuraminidase and thereby allowed hemostatic adaptation that moderated disseminated intravascular coagulation and improved host survival [3]. The ASGPR may therefore be poised for rapid clearance of plasma
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