Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3448-3455
Enhanced Liver Uptake of Opsonized Red Blood Cells After In Vivo
Transfer of Fc
RIIA cDNA to the Liver
Petr Bezdicek,
Stefan Worgall,
Imre Kovesdi,
Moo-Kyung Kim,
Jong-Gu Park,
Theresa Vincent,
Philip L. Leopold,
Alan D. Schreiber, and
Ronald G. Crystal
From the Division of Pulmonary and Critical Care Medicine, Weill
Medical College of Cornell University, New York, NY; GenVec, Inc,
Rockville, MD; InKine Pharmaceutical Co, Inc, Blue Bell, PA; and The
University of Pennsylvania School of Medicine, Philadelphia, PA.
Fc
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 Fc receptor IIA cDNA to convert normally nonphagocytic cells
(hepatocytes) into functional equivalents of phagocytic cells. Ad
vector in vitro transfer and expression of FcRIIA cDNA in primary
rat hepatocytes was confirmed by flow cytometry anti-FcRIIA
immunodetection, and the function of the receptor was demonstrated by
enhanced binding and phagocytosis of 51Cr-labeled
IgG-opsonized erythrocytes. After in vivo gene transfer to rats,
expression of FcRIIA cDNA in hepatocytes was confirmed by Northern
analysis and immunohistochemistry. Rats infected with the Ad vector
carrying the FcRIIA 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 FcRIIA 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.
