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PMID: 11413325 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mononuclear phagocyte differentiation, activation, and viral infection regulate matrix metalloproteinase expression: implications for human immunodeficiency virus type 1-associated dementia.

Journal of virology ·Vol. 75 ·No. 14 ·2001-07-00 ·Pages 6572-83

Ghorpade A, Persidskaia R, Suryadevara R, Che M, Liu XJ, Persidsky Y, Gendelman HE

Abstract

The pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is mediated mainly by mononuclear phagocyte (MP) secretory products and their interactions with neural cells. Viral infection and MP immune activation may affect leukocyte entry into the brain. One factor that influences central nervous system (CNS) monocyte migration is matrix metalloproteinases (MMPs). In the CNS, MMPs are synthesized by resident glial cells and affect the integrity of the neuropil extracellular matrix (ECM). To ascertain how MMPs influence HAD pathogenesis, we studied their secretion following MP differentiation, viral infection, and cellular activation. HIV-1-infected and/or immune-activated monocyte-derived macrophages (MDM) and human fetal microglia were examined for production of MMP-1, -2, -3, and -9. MMP expression increased significantly with MP differentiation. Microglia secreted high levels of MMPs de novo that were further elevated following CD40 ligand-mediated cell activation. Surprisingly, HIV-1 infection of MDM led to the down-regulation of MMP-9. In encephalitic brain tissue, MMPs were expressed within perivascular and parenchymal MP, multinucleated giant cells, and microglial nodules. These data suggest that MMP production in MP is dependent on cell type, differentiation, activation, and/or viral infection. Regulation of MMP expression by these factors may contribute to neuropil ECM degradation and leukocyte migration during HAD.

MeSH Terms
AIDS Dementia Complex/immunology Brain/metabolism Cell Differentiation Cells, Cultured Fetus Humans Immunohistochemistry Leukocytes, Mononuclear/metabolism,physiology,virology Matrix Metalloproteinases/analysis,metabolism Microglia/metabolism,virology Phagocytes/metabolism,physiology,virology
Chemicals
Matrix Metalloproteinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ghorpade A
The Center for Neurovirology and Neurodegenerative Disorders, Department of Pathology and Microbiology, Nebraska Medical Center, Omaha, NE 68198-5215, USA. aghorpade@unmc.edu
Persidskaia R
Suryadevara R
Che M
Liu X J
Persidsky Y
Gendelman H E
References (65)
65 references, click to expand
  1. Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase.
    EMBO J. 1998 May 1;17(9):2607-18 PMID: 9564043
  2. Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1.
    Science. 1990 Dec 14;250(4987):1593-6 PMID: 2148832
  3. Sustained increases in cerebrospinal fluid quinolinic acid concentrations in rhesus macaques (Macaca mulatta) naturally infected with simian retrovirus type-D.
    Brain Res. 1990 Oct 29;531(1-2):148-58 PMID: 1963097
  4. Microglia in human disease, with an emphasis on acquired immune deficiency syndrome.
    Lab Invest. 1991 Feb;64(2):135-56 PMID: 1997729
  5. Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes.
    J Virol. 1991 Aug;65(8):3973-85 PMID: 1830110
  6. Cortical dendritic pathology in human immunodeficiency virus encephalitis.
    Lab Invest. 1992 Mar;66(3):285-91 PMID: 1538584
  7. Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions.
    J Neuropathol Exp Neurol. 1996 Mar;55(3):300-9 PMID: 8786388
  8. Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic window.
    Brain Res. 1995 Dec 12;703(1-2):151-5 PMID: 8719627
  9. Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for CD40-CD40 ligand signaling in atherosclerosis.
    Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1931-6 PMID: 9050882
  10. Matrix metalloproteinases.
    Br J Surg. 1997 Feb;84(2):160-6 PMID: 9052425
  11. Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumour necrosis factor-alpha inhibitor.
    J Neuroimmunol. 1997 Apr;74(1-2):85-94 PMID: 9119983
  12. HIV-I induced destruction of neocortical extracellular matrix components in AIDS victims.
    Neurobiol Dis. 1997;4(3-4):301-10 PMID: 9361307
  13. Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center.
    Ann Neurol. 1997 Dec;42(6):963-72 PMID: 9403489
  14. The neuropathogenesis of the AIDS dementia complex.
    AIDS. 1997;11 Suppl A:S35-45 PMID: 9451964
  15. Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors.
    Ann Neurol. 1998 Jul;44(1):35-46 PMID: 9667591
  16. Cytokine expression in the brain during the acquired immunodeficiency syndrome.
    Ann Neurol. 1992 Apr;31(4):349-60 PMID: 1586135
  17. Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease.
    J Exp Med. 1992 Dec 1;176(6):1703-18 PMID: 1460427
  18. Neutral proteinase expression by human mononuclear phagocytes: a prominent role of cellular differentiation.
    Matrix Suppl. 1992;1:363-7 PMID: 1480061
  19. Stability analysis of latent and active 72-kDa type IV collagenase: the role of tissue inhibitor of metalloproteinases-2 (TIMP-2).
    Biochemistry. 1993 Feb 16;32(6):1583-92 PMID: 8431437
  20. Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia.
    Ann Neurol. 1993 Jun;33(6):576-82 PMID: 8498837
  21. Efficient processing and export of human growth hormone by heat labile enterotoxin chain B signal sequence.
    FEBS Lett. 1993 Sep 6;330(1):61-5 PMID: 8370461
  22. Bacterial collagenase disrupts extracellular matrix and opens blood-brain barrier in rat.
    Neurosci Lett. 1993 Sep 17;160(1):117-9 PMID: 8247322
  23. Role of cytokines and inflammatory mediators in tissue destruction.
    J Periodontal Res. 1993 Nov;28(6 Pt 2):500-10 PMID: 8263720
  24. Expression of metalloproteinases and tissue inhibitors of metalloproteinases in human osteoblast-like cells: differentiation is associated with repression of metalloproteinase biosynthesis.
    Endocrinology. 1994 Jan;134(1):213-21 PMID: 8275936
  25. Elevated central nervous system prostaglandins in human immunodeficiency virus-associated dementia.
    Ann Neurol. 1994 May;35(5):592-7 PMID: 7910004
  26. Platelet-activating factor: a candidate human immunodeficiency virus type 1-induced neurotoxin.
    J Virol. 1994 Jul;68(7):4628-35 PMID: 8207837
  27. A role for extracellular matrix degradation and matrix metalloproteinases in senile dementia?
    Acta Neuropathol. 1994;87(3):308-12 PMID: 8009963
  28. Activation of 72-kDa type IV collagenase/gelatinase by normal fibroblasts in collagen lattices is mediated by integrin receptors but is not related to lattice contraction.
    Exp Cell Res. 1994 Aug;213(2):365-74 PMID: 7519563
  29. Extracellular matrix-degrading proteinases in the nervous system.
    Brain Pathol. 1994 Apr;4(2):145-56 PMID: 8061860
  30. Native TIMP-free 70 kDa progelatinase (MMP-2) secreted at elevated levels by RSV transformed fibroblasts.
    J Cell Physiol. 1994 Dec;161(3):419-28 PMID: 7962125
  31. HIV-1 infection alters monocyte interactions with human microvascular endothelial cells.
    J Immunol. 1995 Jan 1;154(1):422-32 PMID: 7527819
  32. Efficient synthesis of viral nucleic acids following monocyte infection by HIV-1.
    Virology. 1995 Jan 10;206(1):731-5 PMID: 7831833
  33. Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: implications for HIV-associated neurological disease.
    J Exp Med. 1995 Feb 1;181(2):735-45 PMID: 7530762
  34. A regulatory role for astrocytes in HIV-1 encephalitis. An overexpression of eicosanoids, platelet-activating factor, and tumor necrosis factor-alpha by activated HIV-1-infected monocytes is attenuated by primary human astrocytes.
    J Immunol. 1995 Apr 1;154(7):3567-81 PMID: 7897236
  35. T cell gelatinases mediate basement membrane transmigration in vitro.
    J Immunol. 1995 May 1;154(9):4379-89 PMID: 7722295
  36. Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia.
    Ann Neurol. 1995 Nov;38(5):755-62 PMID: 7486867
  37. Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain.
    J Immunol. 1996 Feb 1;156(3):1284-95 PMID: 8558009
  38. Matrix metalloproteinases in brain injury.
    J Neurotrauma. 1995 Oct;12(5):833-42 PMID: 8594211
  39. Presence of matrix metalloproteinase-9 activity in the cerebrospinal fluid of human immunodeficiency virus-infected patients.
    J Infect Dis. 1998 Sep;178(3):854-7 PMID: 9728558
  40. Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms.
    Arterioscler Thromb Vasc Biol. 1998 Oct;18(10):1625-33 PMID: 9763536
  41. Suppression of inflammatory neurotoxins by highly active antiretroviral therapy in human immunodeficiency virus-associated dementia.
    J Infect Dis. 1998 Oct;178(4):1000-7 PMID: 9806027
  42. The role of HIV-1 activated leukocyte adhesion mechanisms and matrix metalloproteinase secretion in AIDS pathogenesis (Review).
    Int J Mol Med. 1998 Feb;1(2):361-6 PMID: 9852238
  43. Human neutrophils secrete gelatinase B in vitro and in vivo in response to endotoxin and proinflammatory mediators.
    Am J Respir Cell Mol Biol. 1999 Mar;20(3):458-64 PMID: 10030844
  44. Regulation of human immunodeficiency virus type 1 infectivity by the ERK mitogen-activated protein kinase signaling pathway.
    J Virol. 1999 Apr;73(4):3460-6 PMID: 10074203
  45. Role of matrix metalloproteinases in models of macrophage-dependent acute lung injury. Evidence for alveolar macrophage as source of proteinases.
    Am J Respir Cell Mol Biol. 1999 Jun;20(6):1145-54 PMID: 10340933
  46. Induction of activator protein 1 (AP-1) in macrophages by human immunodeficiency virus type-1 NEF is a cell-type-specific response that requires both hck and MAPK signaling events.
    J Mol Biol. 1999 Jul 2;290(1):21-35 PMID: 10388555
  47. Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia.
    Ann Neurol. 1999 Sep;46(3):391-8 PMID: 10482270
  48. Influenza A virus infection modulates the expression of type IV collagenase in epithelial cells.
    Arch Virol. 1999;144(7):1361-70 PMID: 10481742
  49. ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by stimulating a cooperative interaction of AP-1 and NF-kappaB.
    J Biol Chem. 1999 Sep 24;274(39):27981-8 PMID: 10488148
  50. Expression of matrix metalloproteinase-9 and its inhibitors in mononuclear blood cells of patients with multiple sclerosis.
    J Neuroimmunol. 1999 Sep 1;99(1):19-26 PMID: 10496173
  51. The matrix metalloprotease matrilysin (PUMP) is expressed in developing human mononuclear phagocytes.
    J Biol Chem. 1992 May 5;267(13):9087-92 PMID: 1374384
  52. Matrix metalloproteinase-9 in peripheral blood eosinophils.
    Int Arch Allergy Immunol. 1999;120 Suppl 1:65-9 PMID: 10529608
  53. Inhibition of matrix metalloproteinase MMP-2 activates chloride current in human airway epithelial cells.
    Can J Physiol Pharmacol. 1999 Jul;77(7):529-35 PMID: 10535713
  54. Microglial and astrocyte chemokines regulate monocyte migration through the blood-brain barrier in human immunodeficiency virus-1 encephalitis.
    Am J Pathol. 1999 Nov;155(5):1599-611 PMID: 10550317
  55. Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation.
    Science. 1999 Dec 17;286(5448):2352-5 PMID: 10600748
  56. Matrix metalloproteinases in early human liver development.
    Histochem Cell Biol. 1999 Oct;112(4):277-82 PMID: 10550612
  57. Increased activity of matrix metalloproteinases in the cerebrospinal fluid of patients with HIV-associated neurological diseases.
    J Neurovirol. 2000 Apr;6(2):156-63 PMID: 10822329
  58. HIV nuclear import: What's the flap?
    Nat Med. 2000 Jun;6(6):626-8 PMID: 10835671
  59. Reduction in glial immunity and neuropathology by a PAF antagonist and an MMP and TNFalpha inhibitor in SCID mice with HIV-1 encephalitis.
    J Neuroimmunol. 2001 Mar 1;114(1-2):57-68 PMID: 11240016
  60. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms.
    Science. 1987 May 15;236(4803):819-22 PMID: 3646751
  61. Distinct biological and serological properties of human immunodeficiency viruses from the brain.
    Ann Neurol. 1988;23 Suppl:S58-61 PMID: 3258140
  62. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes.
    J Exp Med. 1988 Apr 1;167(4):1428-41 PMID: 3258626
  63. Matrix metalloproteinases and diseases of the CNS.
    Trends Neurosci. 1998 Feb;21(2):75-80 PMID: 9498303
  64. Human immunodeficiency virus neurotropism: an analysis of viral replication and cytopathicity for divergent strains in monocytes and microglia.
    J Virol. 1998 Apr;72(4):3340-50 PMID: 9525661
  65. Role of the beta-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia.
    J Virol. 1998 Apr;72(4):3351-61 PMID: 9525662
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.75.14.6572-6583.2001
Email
aghorpade@unmc.edu
Published
2001-07-00
Pages
6572-83
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC114381
Subset
IM
Grants
NINDS NIH HHS · R01 NS036126 · United States
NINDS NIH HHS · R01 NS36126-01 · United States
NINDS NIH HHS · R01 NS32439-01 · United States
NINDS NIH HHS · P01 NS031492 · United States
NIMH NIH HHS · P01 MH57556-01 · United States
NINDS NIH HHS · R01 NS31492-01 · United States
NINDS NIH HHS · R01 NS034239 · United States
External Links
PubMed source DOI: 10.1128/JVI.75.14.6572-6583.2001 PMC Full Text View journal details
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