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Blood, Vol. 93 No. 4 (February 15), 1999:
pp. 1137-1144
RAPID COMMUNICATION
Interferon- Upregulates CCR5 Expression in Cord and Adult Blood
Mononuclear Phagocytes
Deepa Hariharan,
Steven D. Douglas,
Benhur Lee,
Jian-Ping Lai,
Donald E. Campbell, and
Wen-Zhe Ho
From the Divisions of Neonatology and Immunologic and Infectious
Diseases and the Clinical Immunology Laboratories, The Children's
Hospital of Philadelphia, Philadelphia, PA; and the Division of
Pathology and Laboratory Medicine, University of Pennsylvania School of
Medicine, Philadelphia, PA.
The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for
human immunodeficiency virus (HIV) entry into macrophages. The
regulation of their expression influences infectivity by HIV. We report
here that interferon- (IFN-) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5
and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN- showed increased chemotaxis to the CCR5
ligands macrophage inflammatory protein-1 (MIP-1) and MIP-1 , confirming the functional relevance of IFN--induced CCR5
expression. However, IFN- suppressed HIV entry into macrophages.
Interestingly, we demonstrated that IFN- inhibited cell surface
expression of CD4, the major receptor for HIV. This finding may explain
the suppressive effect of IFN- on HIV entry into macrophages,
despite its enhancing effect on the expression of CCR5 and CCR3 by
these cells. In addition, IFN--induced secretion of C-C chemokines (RANTES, MIP-1, and MIP-1) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are
consistent with a novel paradigm in which cytokines regulate HIV
infection and leukocyte migration by reciprocal and opposing effects on
the expression of CD4 and chemokine receptors.
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