Blood, Vol. 90 No. 9 (November 1), 1997:
pp. 3760-3765
Human Immunodeficiency Virus-1 env Impairs Fc
Receptor-Mediated Phagocytosis Via a Cyclic Adenosine Monophosphate-Dependent Mechanism
By
Christian A. Thomas,
Ofra K. Weinberger,
Benedikt L. Ziegler,
Steven Greenberg,
Ira Schieren,
Samuel C. Silverstein, and
Joseph El Khoury
From the Departments of Physiology and Cellular Biophysics, Medicine, and The Howard Hughes Medical Institute, Columbia University, New York; the Department of Medicine, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY; and the Department of Hematology and Oncology, University of Tübingen, Tübingen, Germany.
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ABSTRACT |
Human immunodeficiency virus (HIV)-1 expression in mononuclear phagocytes is associated with multiple functional defects, including phagocytosis. To assess Fc
receptor (FcR) function in cells expressing HIV-1, human promonocytic cells (U937) acutely or chronically infected with HIV-1, or stably transfected with a noninfectious reverse transcriptase (RT) defective HIV-1 provirus (
pol), were treated with phorbol 12-myristate 13-acetate for 48 hours and tested for their ability to ingest sheep erythrocytes coated with IgG (E-IgG). HIV-1-infected or transfected U937 cells ingested 50% to 65% fewer E-IgG than controls despite normal surface expression of FcRs. HIV-1 specifically impaired FcR-mediated phagocytosis, as ingestion of complement-coated erythrocytes was unaffected. U937 cells transfected with an env deficient mutant of HIV-1 ingested E-IgG normally, suggesting that the expression of HIV-1 env was required for HIV-1 to inhibit FcR-mediated phagocytosis. Expression of HIV-1 in U937 cells was associated with an increased accumulation of intracellular cyclic adenosine monophosphate (cAMP); addition of the adenylate cyclase inhibitor 2',5'-dideoxyadenosine to these cells decreased intracellular cAMP levels to that of controls and restored FcR-mediated phagocytosis. Addition of either interferon (IFN)-
or an inhibitor of cAMP-dependent protein kinase A (KT 5720) to HIV-1-transfected U937 cells also restored FcR-mediated phagocytosis. Expression of HIV-1 induces a specific defect of FcR function in mononuclear phagocytes that correlates with increased levels of cAMP, and can be corrected by pharmacologic manipulation.
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INTRODUCTION |
INFECTION WITH human immunodeficiency virus (HIV)-1 leads to a profound and progressive state of immune deficiency, particularly in the number and function of CD4+ lymphocytes.1 Mononuclear phagocytes are also targets of HIV-12 and may serve as reservoirs for HIV-1.3-5 While the viral burden of circulating blood mononuclear cells is low (0.0025% to 2.5% of cells are infected) consisting mostly of CD4+ lymphocytes,6,7 the percentage of tissue macrophages infected with HIV-1 is appreciable, particularly in the brain (1% to 10%),8,9 lymph nodes (10%),10 and the lung (10% to 50%).11 This raises the question of whether expression of HIV-1 has direct deleterious effects on macrophage function.
Receptors for the Fc portion of IgG (Fc receptors; Fc Rs) mediate phagocytosis of IgG-opsonized particles and clearance of immune complexes. In HIV-1-infected patients, clearance of IgG-coated erythrocytes is impaired,12 suggesting a decline in FcR function in patients with acquired immune deficiency syndrome (AIDS). Furthermore, mononuclear phagocytes from HIV-1-infected patients have decreased FcR function in vitro.13-15 This decline in receptor function may have important consequences for host defense and susceptibility to infections, and may reflect direct or indirect effects of HIV-1 infection. It is not clear whether decreased FcR function reflects decreased surface expression of FcRs, as suggested by a study using monocyte-derived macrophages infected with HIV-1 in vitro16 or abnormally functioning surface FcRs, because FcR expression on monocytes isolated from HIV-infected individuals is reportedly normal.14,17
The aim of this study was to assess the direct effect of HIV-1 expression on FcR-mediated phagocytosis. To avoid working with heterogeneous cell populations (ie, consisting of HIV-infected and uninfected cells), we studied U937 cells (a human mononuclear phagocyte cell line), which were latently infected with HIV-1 or expressed HIV-1 gene products. Our results indicate that infection with HIV-1 leads to impairment of FcR-mediated phagocytosis, and that this impairment is mediated by accumulation of cyclic adenosine monophosphate (cAMP).
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MATERIALS AND METHODS |
Cells.
U937 cells were obtained from the American Type Tissue Collection (Rockville, MD) and U1 cells were obtained from the AIDS Research and Reference Reagent Program (Bethesda, MD) and are described elsewhere.18,19 Upol cells were generated by electroporation of 107 U937 cells with 5 mg of pHXBpol, a noninfectious proviral plasmid.20 A deletion in the pol coding region abrogates reverse transcriptase (RT) activity of Upol cells; consequently, cells transfected pHXBpol express HIV-1 proteins, but do not produce infectious virions. Uenv cells were generated by transfection of U937 cells with an env deficient mutant of pol. 21 U937/LAV cells are U937 cells that survived acute infection with HIV-1 (strain LAV) and produce high constitutive levels of HIV-1 as determined by RT assay.
Phagocytosis assays.
A total of 2.5 × 105 U937 cells were incubated in 12-well dishes at 37°C for 48 hours in RPMI 1640 (Life Technologies, Grand Island, NY) supplemented with 10% fetal calf serum (Intergen, Purchase, NY) and 40 nmol/L phorbol 12-myristate 13-acetate (PMA; Sigma, St Louis, MO) to induce differentiation to a phagocytic phenotype.22 Interferon (IFN)- (Collaborative Biomedical Products, Bedford, MA), 2',5'-dideoxyadenosine (ddAdo; Pharmacia, Piscataway, NJ), or KT 5720 (Calbiochem, La Jolla, CA) were added at the indicated concentrations. After 48 hours, sheep erythrocytes opsonized with IgG23 or C3bi24 were added for 1 hour at 37°C, the cells were washed, fixed in 3.7% formaldehyde, and stained with acridine orange (10 µg/mL) for 20 minutes to distinguish bound from ingested opsonized erythrocytes.23 The phagocytic index (PI) was determined by counting the number of ingested erythrocytes per 100 macrophages, as described.23 Percent phagocytosing cells denotes the number of cells that ingested 
1 target. Some results were expressed in percent of the PI of uninfected U937 controls.
cAMP measurements.
A total of 5 × 106 adherent U937, U1, Upol, or Uenv cells incubated with 40 nmol/L PMA as described above were used for determination of cAMP content. Measurements of intracellular cAMP were performed using a commercially available assay (Amersham, Arlington Heights, IL) according to manufacturer's recommendations.
Cell surface FcR expression.
A total of 106 U937, U1, or Upol cells were incubated with 40 nmol/L PMA as described and stained with the following fluorescein isothiocyanate (FITC)-labeled antibodies, or isotype-matched controls, for 20 minutes at 4°C: monoclonal antibody (MoAb) 32.2 (anti-Fc RI), MoAb IV.3 (anti-FcRII), or MoAb 3G8 (anti-Fc RIII), all from Medarex (Annandale, NJ). Flow cytometry analyses were performed on a Coulter Epics 753 (Coulter Corp, Miami, FL).
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RESULTS |
Expression of HIV-1 in U937 cells decreases phagocytosis of E-IgG, but not of E-C3bi.
We measured the ability of U937 cells, which were acutely (U937/LAV) or chronically (U1) infected with HIV-1 or transfected with a noninfectious HIV-1 provirus (Upol), to ingest E-IgG. To render U937 cells capable of phagocytosis, we incubated them with 40 nmol/L PMA for 48 hours before each experiment.22 The phagocytic indices of U937/LAV and U1 cells and three different Upol cell clones were decreased by 51% to 66% compared with U937 control cells (Table 1). Similarly, the ability of HIV-1-infected or transfected U937 cells to ingest 1 or more E-IgG was decreased by 27% to 64% compared with U937 control cells. The impairment of phagocytosis was not due to decreased surface expression of Fc receptors, as flow cytometry showed equivalent levels of surface expression of FcRI and II (Fig 1). Consistent with earlier findings,25 we could not detect surface expression of FcR III in U937 cells (not shown).
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| Fig 1.
Surface expression of FcR I and II in U937, Upol, and U1 cells. Flow cytometry of the indicated cells incubated with anti-FcR IgG was performed after a 48-hour incubation with 40 nmol/L PMA. The left curves represent cells incubated with FITC-labeled isotype matched control antibodies.
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To test whether the phagocytic impairment was specific for Fc receptors, erythrocytes opsonized with C3bi (E-C3bi) were used as alternative phagocytic targets. Upol cells ingested equal numbers of E-C3bi compared with U937 control cells (Fig 2). In a separate experiment, phagocytosis of E-C3bi by U937 or Upol cells was inhibited by >90% in the presence of EDTA, consistent with earlier findings that ingestion of E-C3bi was mediated primarily by complement receptor-3 (Mac-1/
M
2 ) and requires the presence of divalent cations.26
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| Fig 2.
Expression of HIV-1 does not affect phagocytosis of E-C3bi. Phagocytosis assays were performed as described in Materials and Methods. The mean phagocytic indices of untransfected U937 control cells for E-IgG and E-C3bi were 237 ± 21 and 176 ± 15, respectively. Data represent the mean ± standard error of mean (SEM) (n = 3).
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HIV-1 Env decreases the phagocytic capacity of U937 cells.
The envelope glycoprotein of HIV-1 (gp120) has been reported to impair various cellular functions.15,27-30 To test whether expression of HIV-1 env in U937 cells affects FcR function, we assessed E-IgG phagocytosis in U937 cells transfected with a pol construct that is env deficient (pol-env).21 U937pol-env cells showed levels of phagocytosis of E-IgG that equaled or exceeded that of U937 control cells (Fig 3). Thus, one or more products of the env gene is required for the impairment in Fc receptor-mediated phagocytosis by HIV-1.
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| Fig 3.
Impairment of FcR-mediated phagocytosis requires HIV-1 env. Ingestion of E-IgG was performed as described in Materials and Methods using U937 cells and three different Upol and Uenv clones. Data represent the mean ± SEM (n = 6).
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Inhibition of intracellular cAMP formation or cAMP-dependent protein kinase restores the phagocytic capacity of Upol cells.
Addition of a cell-permeant analog of cAMP decreased FcR-mediated phagocytosis in U937 cells (Fig 4A), consistent with other reports.31,32 We reasoned that expression of HIV-1 env might decrease FcR-mediated phagocytosis through a cAMP-dependent mechanism. Intracellular cAMP levels were four times higher in Upol cells and 12 times higher in U1 cells compared with nontransfected U937 cells or pol-env transfected U937 cells (Fig 4B), similar to results of a previous study33 using a T-lymphoblast cell line. Addition of the adenylate cyclase inhibitor ddAdo decreased intracellular cAMP content (Fig 4C) of Upol cells and restored FcR-mediated phagocytosis of these cells to control levels (Fig 4D).
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| Fig 4.
cAMP inhibits Fc R-mediated phagocytosis in U937 cells. (A) Phagocytosis of E-IgG by U937 cells was performed after preincubation for 48 hours in the presence of the indicated concentrations of 8-bromoadenosine-3':5'-cyclic-monophosphate and 40 nmol/L PMA. (B) cAMP levels in HIV-1-expressing U937 cells and controls. (C) cAMP levels in the indicated cell lines incubated for 48 hours in the absence or presence of the adenylate cyclase inhibitor, 2'-5'-dideoxyadenosine. (D) Phagocytosis of E-IgG by either U937 or Upol cells incubated for 48 hours in the absence or presence of the adenylate cyclase inhibitor, 2'-5'-dideoxyadenosine. Data represent the mean ± SEM of three to six experiments.
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Many of the intracellular actions of cAMP are mediated by cAMP-dependent protein kinase (PKA). We tested whether the decrease in FcR-mediated phagocytosis in Upol cells was reversed by inhibition of PKA activity. Addition of the PKA inhibitor KT 572034 to Upol cells restored FcR-mediated phagocytosis to control levels (Fig 5), but did not significantly affect the phagocytic capacity of nontransfected U937 cells (not shown).
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| Fig 5.
The PKA inhibitor KT5720 restores phagocytosis of E-IgG by Upol cells. Phagocytosis assays were performed with the indicated concentrations of the PKA inhibitor KT5720 as described in Materials and Methods. Data represent the mean ± SEM (n = 3).
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IFN- restores the phagocytic capacity of Upol cells.
IFN- has been shown to increase human monocyte phosphodiesterase activity35 and to downregulate membrane adenylate cyclase activity,36 both of which might decrease intracellular cAMP concentrations. We incubated PMA-treated Upol cells with or without IFN- for 48 hours and quantitated phagocytosis of E-IgG. Addition of IFN- decreased intracellular cAMP concentrations and increased phagocytosis of E-IgG by Upol cells (Fig 6), and U1 cells (not shown), whereas it had no significant effect on phagocytosis of E-IgG by nontransfected U937 cells. Flow cytometry showed that IFN- treatment did not increase expression of FcRIs and FcRIIs in PMA-treated Upol and U1 cells (not shown).
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| Fig 6.
Restoration of FcR-mediated phagocytosis by IFN-. Phagocytosis of E-IgG by Upol cells and intracellular cAMP concentrations were measured as described in Materials and Methods after incubation for 48 hours with the indicated concentrations of recombinant IFN-. Data represent the mean ± SEM (n = 3).
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DISCUSSION |
HIV-1 infection is associated with multiple functional defects in mononuclear phagocytes,2 such as decreases in chemotactic activity,27,37-39 clearance of IgG-labeled targets,12 antigen presentation,40 and intracellular killing of Candida spp.,41,42 Toxoplasma gondii,43,44 and Aspergillus fumigatus.45 Diminished phagocytosis of a variety of particulate targets by mononuclear phagocytes from HIV-1-positive individuals has been reported in some,12-14 but not all studies.39,46,47 Some of these differences may reflect heterogeneity in the cell population studied, possibly as a result of using cells from patients at different stages of HIV-1 infection and/or with different viral burdens. For example, production of viral proteins p24 and gp120 was undetectable in alveolar macrophages from 15 HIV-1-positive patients.48 When cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor (TNF )-, 30% to 60% of cells from these patients produced viral proteins and 60% to 80% expressed viral RNA,48 suggesting that the majority of theses cells are latently infected. In addition, viral burden increases with progression from the asymptomatic carrier state to AIDS.1,49,50 Similarly, heterogeneity in the population of infected cells also occurs in primary cells infected with HIV-1 in vitro, as virus expression varies from 28%16 to 75%51 of cells after infection with HIV-1 in vitro. Therefore, the use of a uniform population of HIV-1-expressing mononuclear phagocytes, as described in this study, tests the direct effect of HIV-1 on phagocytic function. These cells may serve as a model system to study the effects of HIV-1 on tissue macrophages, particularly during advanced stages of the disease.
Little is known about the mechanisms by which HIV-1 causes alterations of mononuclear phagocyte function. In the present study, we show that expression of HIV-1 env impairs Fc receptor-mediated phagocytosis, which is correlated with an enhanced accumulation of cAMP, an effect which is reversed by agents that inhibit cAMP production or that block its effects. These findings are consistent with reported depressant effects of cAMP on phagocytosis by an unknown mechanism.31,32 Precisely how expression of HIV-1 leads to increased accumulation of cAMP is not known, but our data suggest an involvement of HIV-1 env (Fig 4B). Perhaps binding of gp120 to CD4 or its coreceptor, CCR-5, a member of the chemokine receptor family, activates adenylate cyclase by stimulating a G protein. Interestingly, addition of macrophage inflammatory protein 1 alpha (MIP-1), a known ligand of CCR-5, to the human M07e cell line enhances the cAMP content of these cells52 and exposure to picomolar concentrations of gp120 increases the cAMP content of microglial cells.53 We envision that expression of HIV-1 env leads to decreased phosphodiesterase activity and/or upregulation of adenylate cyclase activity, both of which can be reversed by IFN-.35,36 This may explain our finding that IFN- restores FcR-mediated phagocytosis in HIV-1-expressing cells. Elucidating the cellular changes that accompany HIV-1 infection of mononuclear phagocytes may lead to the development of new therapeutic strategies for the treatment of the immune defects that are characteristic of HIV-1 infection.
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FOOTNOTES |
Submitted February 7, 1997;
accepted July 3, 1997.
Supported by an Investigatorship from Arthur N. Saydman Trust Fund, New York, NY for Research in Septicemia in honor of Dr Harold C. Neu at Columbia University (to C.A.T.); a Research Fellowship from the Lucille P. Markey Charitable Trust, Miami, FL (to C.A.T.); Grant No. HL54164 (to S.G.), Grant No. AI20516 (to S.C.S), and Grant No. HL43528 (to D.K.W.) from the National Institutes of Health, Bethesda, MD; Grant No. FI4P-CT95-0029 from the European Communities, Brussels, Belgium (to B.L.Z); and Grant No. E/B41G/T0347/T5920 from the German Ministry of Defense, Bonn, Germany (to B.L.Z). S.G. is an Established Investigator of the American Heart Association.
Address reprint requests to Christian A. Thomas, MD, Division of Medical Oncology, Columbia Presbyterian Medical Center, MHB-6-435, 177 Ft Washington Ave, New York, NY 10032.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hearly marked
``advertisment'' in accordance with 18 U.S.C. section 1734 solely to
indicate this fact.
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REFERENCES |
1.
Fauci AS:
The human immunodeficiency virus: Infectivity and mechanisms of pathogenesis.
Science
239:617,
1988[Abstract/Free Full Text]
2.
Meltzer MS,
Gendelman HE:
Mononuclear phagocytes as targets, tissue reservoirs, and immunoregulatory cells in human immunodeficiency virus disease.
Curr Topics Microbiol Immunol
182:239,
1992
3.
Bender BS,
Davidson BL,
Kline R,
Brown C,
Quinn TC:
Role of the mononuclear phagocyte system in the immunopathogenesis of human immunodeficiency virus infection and the acquired immunodeficiency syndrome.
Rev Infect Dis
10:1142,
1988[Medline]
[Order article via Infotrieve]
4.
Gendelman HE,
Orenstein JM,
Baca LM,
Weiser B,
Burger H,
Kalter DC,
Meltzer MS:
The macrophage in the persistence and pathogenesis of HIV infection.
AIDS
3:475,
1989[Medline]
[Order article via Infotrieve]
5.
Meltzer MS,
Skillman DR,
Hoover DL,
Hanson BD,
Turpin JA,
Kalter DC,
Gendelman HE:
Macrophages and the human immunodeficiency virus.
Immunol Today
11:217,
1990[Medline]
[Order article via Infotrieve]
6.
Schnittman SM,
Psallidopoulos MC,
Lane HC,
Thompson L,
Baseler B,
Massari F,
Fox CH,
Salzman NP,
Fauci AS:
The reservoir for HIV-1 in human peripheral blood is a T-cell that maintains expression of CD4.
Science
245:305,
1989[Abstract/Free Full Text]
7.
Psallidopoulos MC,
Schnittman SM,
Thompson LM,
Baseler B,
Fauci AS,
Lane HC,
Salzman NP:
Integrated proviral human immunodeficiency type I is present in CD4+ peripheral blood lymphocytes in healthy seropositive individuals.
J Virol
63:4626,
1989[Abstract/Free Full Text]
8.
Stoler MH,
Eskin TA,
Benn S,
Angerer RC,
Angerer LM:
Human T-cell lymphotropic virus type III infection of the central nervous system. Preliminary in situ analysis.
JAMA
6:2360,
1986
9.
Koenig S,
Gendelman HE,
Orenstein JM,
Dal Canto MC,
Pezeshkpour GM,
Yungbluth M,
Janotta F,
Aksamit A,
Martin MA,
Fauci AS:
Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy.
Science
233:1089,
1986[Abstract/Free Full Text]
10.
Gyorkey F,
Melnick JL,
Sinkovics JG,
Gyorkey P:
Retrovirus resembling HTLV in macrophages of patients with HIV.
Lancet
1:106,
1985[Medline]
[Order article via Infotrieve]
11.
Plata F,
Autran B,
Martins LP,
Wain-Hobson S,
Raphael M,
Mayaud C,
Denis M,
Guillon J-M:
AIDS virus-specific cytotoxic T lymphocytes in lung disorders.
Nature
328:348,
1987[Medline]
[Order article via Infotrieve]
12.
Bender BS,
Frank MM,
Lawley TJ,
Smith WJ,
Brickman CM,
Quinn TC:
Defective reticuloendothelial system Fc-receptor function in patients with acquired immunodeficiency syndrome.
J Infect Dis
152:409,
1985[Medline]
[Order article via Infotrieve]
13.
Capsoni F,
Minonzio F,
Ongari AM:
Increased expression of IgG Fc receptor on neutrophils and monocytes from HIV-1 infected subjects.
Clin Exp Immunol
90:175,
1992[Medline]
[Order article via Infotrieve]
14.
Capsoni F,
Minonzio F,
Ongari AM,
Bonara P,
Pinto G,
Carbonelli V,
Lazzarin A,
Zanussi C:
Fc receptor expression and function in mononuclear phagocytes from AIDS patients: Modulation by IFN-gamma.
Scand J Immunol
39:45,
1994[Medline]
[Order article via Infotrieve]
15.
Duerrbaum-Landmann I,
Klatenhaeuser E,
Flad H-D,
Ernst M:
HIV-1 envelope protein gp120 affects phenotype and function of monocytes in vitro.
J Leukoc Biol
55:545,
1994[Abstract]
16.
Kent SJ,
Stent G,
Sonza S,
Hunter SD,
Crowe SM:
HIV-1 infection of monocyte derived macrophages reduces Fc and complement receptor expression.
Clin Exp Immunol
95:450,
1994[Medline]
[Order article via Infotrieve]
17.
Davidson BL,
Kline RL,
Rowland J,
Quinn TC:
Surface markers of monocyte function and activation in AIDS.
J Infect Dis
158:483,
1988[Medline]
[Order article via Infotrieve]
18.
Sundstroem C,
Nilsson K:
Establishment and characterization of a human histiocytic lymphoma cell line (U-937).
Int J Cancer
17:565,
1976[Medline]
[Order article via Infotrieve]
19.
Folks TM,
Justement J,
Kinter A,
Dinarello CA,
Fauci AS:
Cytokine-induced expression of HIV-1 in a chronically infected promonocytic cell line.
Science
238:800,
1987[Abstract/Free Full Text]
20.
Marcuzzi A,
Weinberger J,
Weinberger OK:
Transcellular activation of the human immunodeficiency virus type 1 long terminal repeat in cocultured lymphocytes.
J Virol
667:4228,
1992
21.
Marcuzzi A,
Lowy I,
Weinberger OK:
Transcellular activation of the human immunodeficiency virus type 1 long terminal repeat in T lymphocytes requires CD4-gp120 binding.
J Virol
66:4536,
1992[Abstract/Free Full Text]
22.
Nambu M,
Morita M,
Watanabe H,
Uenoyama Y,
Kim K,
Tanaka M,
Iwai Y,
Kimata H,
Mayumi M,
Mikawa H:
Regulation and Fc receptor expression and phagocytosis of a human monoblast cell line U937: Participation of cAMP and protein kinase C in the effects of IFN- and phorbol ester.
J Immunol
143:4158,
1989[Abstract]
23.
Greenberg S,
El Khoury J,
Kaplan E,
Silverstein SC:
A fluorescence technique to distinguish attached from ingested erythrocytes and zymosan particles in phagocytosing macrophages.
J Immunol Methods
139:115,
1991[Medline]
[Order article via Infotrieve]
24.
Wright SD,
Tobias PS,
Ulevitch RJ,
Ramos RA:
Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages.
J Exp Med
170:1231,
1989[Abstract/Free Full Text]
25.
Unkeless JC,
Scigliano E,
Freedman VH:
Structure and function of human and murine receptors for IgG.
Ann Rev Immunol
6:251,
1988[Medline]
[Order article via Infotrieve]
26.
Wright SD,
Silverstein SC:
Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes.
J Exp Med
156:1149,
1982[Abstract/Free Full Text]
27.
Wahl SM,
Allen JB,
Gartner S,
Orenstein JM,
Popovic M,
Chenoweth DE,
Arthur LO,
Farrar WL,
Wahl LM:
HIV-1 and its envelope glycoprotein downregulate chemotactic ligand receptors and chemotactic function of peripheral blood monocytes.
J Immunol
142:3553,
1989[Abstract]
28.
Mann DL,
Gartner S,
leSane F,
Buchow H,
Popovic M:
HIV-1 transmission and function of virus-infected monocytes/macrophages.
J Immunol
144:2152,
1990[Abstract]
29.
Wagner RP,
Levitz SM,
Tabuni A,
Kornfeld H:
HIV-1 envelope protein (gp120) inhibits the activity of human bronchoalveolar macrophages against Cryptococcus neoformans.
Am Rev Resp Dis
146:1434,
1992[Medline]
[Order article via Infotrieve]
30.
Shiratsuchi H,
Johnson JL,
Toossi Z,
Ellner JJ:
Modulation of the effector function of human monocytes for Mycobacterium avium by human immunodeficiency virus-1 envelope glycoprotein gp120.
J Clin Invest
93:885,
1994
31.
Cox JP,
Karnovsky ML:
The depression of phagocytosis by exogenous cyclic nucleotides, prostaglandins, and theophylline.
J Cell Biol
59:480,
1973[Abstract/Free Full Text]
32.
Wirth JJ,
Kierszenbaum F:
Inhibitory action of elevated levels of adenosine-3':5' cyclic monophosphate on phagocytosis: Effects on macrophage-Trypanosoma cruzi interaction.
J Immunol
129:2759,
1982[Abstract]
33.
Nokta M,
Pollard R:
Human immunodeficiency virus infection: Association with altered intracellular levels of cAMP and cGMP in MT-4 cells.
Virology
181:211,
1991[Medline]
[Order article via Infotrieve]
34.
Gadbois DM,
Crissman HA,
Tobey RA,
Bradbury EM:
Multiple kinase arrest points in the G1 phase of nontransformed mammalian cells are absent in transformed cells.
Proc Natl Acad Sci USA
89:8626,
1992[Abstract/Free Full Text]
35.
Li S-H,
Chan SC,
Toshitani A,
Leung DYM,
Hanifin JM:
Synergistic effects of interleukin 4 and interferon gamma on monocyte phosphodiesterase activity.
J Invest Dermatol
99:65,
1992[Medline]
[Order article via Infotrieve]
36.
Adachi I,
Connolly N,
Suzuki T:
Interferon-gamma down-regulates membrane adenylate cyclase activity of a murine macrophage-like cell line (P388D1).
Cytokine
1:36,
1989[Medline]
[Order article via Infotrieve]
37.
Ras GJ,
Eftychis HA,
Anderson R,
Van Der Walt I:
Mononuclear and polymorphonuclear leukocyte dysfunction in male homosexual with the acquired immunodeficiency syndrome (AIDS).
S Afr Med J
66:806,
1984[Medline]
[Order article via Infotrieve]
38.
Smith PD,
Ohura K,
Masur H,
Lane HC,
Fauci AS,
Wahl SM:
Monocyte-macrophage function in the acquired immune deficiency syndrom: Defective chemotaxis.
J Clin Invest
74:2121,
1984
39.
Poli G,
Botazzi B,
Acero R:
Monocyte function in intravenous drug abusers with lymphadenopathy syndrome: Selective impairment of chemotaxis.
Clin Exp Immunol
62:136,
1985[Medline]
[Order article via Infotrieve]
40.
Prince H,
Moody D,
Shubin B,
Fahey JL:
Defective monocyte function in acquired immune deficiency syndrome (AIDS): Evidence from a monocyte dependent T-cell proliferative system.
J Clin Immunol
5:21,
1985[Medline]
[Order article via Infotrieve]
41.
Washburn RG,
Tuazon CU,
Bennett JE:
Phagocytic and fungicidal activity of monocytes from patients with acquired immunodeficiency syndrome.
J Infect Dis
151:565,
1985[Medline]
[Order article via Infotrieve]
42.
Baldwin GC,
Fleischmann J,
Chung Y,
Koynagi Y,
Chen ISY,
Golde DW:
Human immunodeficiency virus causes mononuclear phagocyte dysfunction.
Proc Natl Acad Sci USA
87:3933,
1990[Abstract/Free Full Text]
43.
Eales LJ,
Moshtael O,
Pinching AJ:
Microbicidal activity of monocyte derived macrophages in AIDS and related disorders.
Clin Exp Immunol
67:227,
1987[Medline]
[Order article via Infotrieve]
44.
Biggs B-A,
Hewish M,
Kent S,
Hayes K,
Crowe S:
HIV-1 infection of human macrophages impairs phagocytosis and killing of Toxoplasma gondii.
J Immunol
154:6132,
1995[Abstract]
45.
Roilides E,
Holmes A,
Blake C,
Pizzo PA,
Walsh TJ:
Defective antifungal activity of monocyte-derived macrophages from human immunodeficiency virus-infected children against Aspergillus fumigatus.
J Infect Dis
168:1562,
1993[Medline]
[Order article via Infotrieve]
46.
Nielsen H,
Kharazmi A,
Faber V:
Blood monocyte and neutrophil functions in the acquired immune deficiency syndrome.
Scand J Immunol
24:291,
1986[Medline]
[Order article via Infotrieve]
47.
Estevez ME,
Ballart IJ,
Diez RA,
Planes N,
Scaglione C,
Sen L:
Early defect of phagocytic cell function in subjects at risk for acquired immunodeficiency syndrome.
Scand J Immunol
24:215,
1986[Medline]
[Order article via Infotrieve]
48.
Lebargy F,
Branellec A,
Deforges L,
Bignon J,
Brnaudin J-F:
HIV-1 in human alveolar macrophages from infected patients is latent in vivo but replicates after in vitro stimulation.
Am J Resp Cell Mol Biol
10:72,
1994[Abstract]
49.
Piatak M Jr,
Saag MS,
Yang LC,
Clark SJ,
Kappes JC,
Luk K-C,
Hahn BH,
Shaw GM,
Lifson JD:
High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR.
Science
259:1749,
1993
50.
Ho DD,
Moudgil T,
Alam M:
Quantitation of human immunodeficiency virus type I in the blood of infected persons.
N Engl J Med
321:1621,
1989[Abstract]
51.
Nottet HSLM,
deGraaf L,
deVos NM,
Bakker LJ,
vanStrijp JAG,
Visser MR,
Verhoef J:
Phagocytic function of monocyte-derived macrophages is not affected by human immunodeficiency virus type 1 infection.
J Infect Dis
168:84,
1993[Medline]
[Order article via Infotrieve]
52.
Mantel C,
Aronica S,
Luo Z,
Marshall MS,
Kim YJ,
Cooper S,
Hague N,
Broxmeyer HE:
Macrophage inflammatory protein-1 alpha enhances growth factor-stimulated phosphatidyl-choline metabolism and increases cAMP levels in the human growth factor-dependent cell line MO7e, events associated with growth suppression.
J Immunol
154:2342,
1995[Abstract]
53.
Levi G,
Patrizio M,
Bernardo A,
Petrucci TC,
Agresti C:
Human immunodeficiency virus coat protein gp120 inhibits the -adrenergic regulation of astroglial and microglial functions.
Proc Natl Acad Sci USA
90:1541,
1993[Abstract/Free Full Text]
Abstract
Introduction
Abstract
