Enhanced Liver Uptake of Opsonized Red Blood Cells After In Vivo Transfer of FcγRIIA cDNA to the Liver

Abstract

Fcγ receptors convey to phagocytic cells the ability to recognize, bind, and internalize IgG-coated cells and microorganisms. The present study demonstrates the use of adenovirus (Ad)-mediated gene transfer of human Fcγ receptor IIA cDNA to convert normally nonphagocytic cells (hepatocytes) into functional equivalents of phagocytic cells. Ad vector in vitro transfer and expression of FcγRIIA cDNA in primary rat hepatocytes was confirmed by flow cytometry anti-FcγRIIA immunodetection, and the function of the receptor was demonstrated by enhanced binding and phagocytosis of (51)Cr-labeled IgG-opsonized erythrocytes. After in vivo gene transfer to rats, expression of FcγRIIA cDNA in hepatocytes was confirmed by Northern analysis and immunohistochemistry. Rats infected with the Ad vector carrying the FcγRIIA cDNA demonstrated enhanced clearance of opsonized erythrocytes, but not nonopsonized erythrocytes, from the circulation with increased sequestration within the liver. Together, these data demonstrate that Ad-mediated FcγRIIA gene transfer can convert normally IgG-nonphagocytic cells into phagocytic cells capable of recognizing, binding, and ingesting an opsonized particulate antigen, suggesting that gene transfer strategies might be used to transiently augment host defense by enhancing the clearance of immune complexes.