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Blood, Vol. 93 No. 6 (March 15), 1999:
pp. 1851-1857
Human Immunodeficiency Virus Replication Induces Monocyte Chemotactic
Protein-1 in Human Macrophages and U937 Promonocytic Cells
Manuela Mengozzi,
Camilla De Filippi,
Pietro Transidico,
Priscilla Biswas,
Manuela Cota,
Silvia Ghezzi,
Elisa Vicenzi,
Alberto Mantovani,
Silvano Sozzani, and
Guido Poli
From the AIDS Immunopathogenesis Unit, DIBIT, San Raffaele Scientific
Institute, Milano; the Department of Immunology and Cell Biology,
"Mario Negri" Institute for Pharmacological Research, Milano; and
the Section of Pathology and Immunology, Department of Biotechnology,
University of Brescia, Brescia, Italy.
We have recently described a significant correlation between human
immunodeficiency virus-1 (HIV-1) RNA replication and monocyte chemotactic protein-1 (MCP-1) levels in the cerebrospinal fluid (CSF)
of individuals with the acquired immunodeficiency syndrome (AIDS) with
HIV encephalitis (E). Because local macrophages (microglia) are the
cells predominantly infected in the brain, we investigated whether in
vitro HIV infection affects MCP-1 production in mononuclear phagocytes
(MP). MCP-1 secretion and expression were consinstently upregulated
over constitutive levels in human monocyte-derived macrophages (MDM)
infected with the M-tropic R5 BaL strain of HIV-1. HIV replication was
required for this effect, as demonstrated by the absence of chemokine
upregulation after infection in the presence of
3'-azido-3'-deoxythimidine (AZT) or cell-exposure to heat-inactivated
( °) virus. MCP-1 induction was not restricted to HIV-1 BaL, but
was also observed during productive infection of MDM with two primary
isolates differing for entry coreceptor usage and of U937 cells with
the X4 HIV-1 MN strain. Based on the observation that exogenous HIV-1
Tat induced MCP-1 expression in astrocytes, we also investigated its
role in MDM and U937 cells. Exogenous Tat induced MCP-1 production from
MDM in a concentration-dependent manner, however, it was not effective
on uninfected U937 cells or on the chronically infected U937-derived
cell line U1. Transfection of Tat-expressing plasmids moderately
activated HIV expression in U1 cells, but failed to induce MCP-1
expression in this cell line or in uninfected U937 cells. HIV
replication-dependent expression of MCP-1 in MP may be of particular
relevance for the pathogenesis of HIV infection in nonlymphoid organs
such as the brain.
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