       Document 0500
 DOCN  M9630500
 TI    HIV-1 gp160 protein-macrophage interactions modulate mesangial cell
       proliferation and matrix synthesis.
 DT    9603
 AU    Singhal PC; Sharma P; Garg P; Department of Medicine, Long Island Jewish
       Medical Center, New; Hyde Park, NY 11042, USA.
 SO    Am J Pathol. 1995 Dec;147(6):1780-9. Unique Identifier : AIDSLINE
       MED/96094761
 AB    Patients with HIV infection often develop glomerular lesions (focal
       segmental glomerular sclerosis). Because mesangial expansion (enhanced
       mesangial cell (MC) growth and matrix accumulation) has been
       demonstrated to precede the development of focal segmental
       glomerulosclerosis, we studied the effect of the interaction between
       HIV-1 proteins such as gp160 envelope protein and macrophages on
       mesangial cell proliferation and matrix synthesis. We determined the
       effect of control media, serum-free macrophage supernatant (MSP), and
       serum-free HIV-1 gp 160 protein-treated MSP (gp 160-MSP) on the
       proliferation of MC and synthesis of collagen type IV (a component of
       mesangial matrix). MSP (20%) enhanced (P < 0.01) MC proliferation
       (control, 7.58 +/- 0.29 versus MSP, 9.06 +/- 0.25 x 10(4) cells/ml),
       whereas gp 160-MSP (20%) inhibited (P < 0.001) MC proliferation
       (gp160-MSP, 5.58 +/- 0.14 x 10(4) cells/ml). gp160-MSP modulated MC
       proliferation in a dose-dependent manner; it enhanced cell proliferation
       at a lower concentration but inhibited cell proliferation at a higher
       concentration. Anti-TGF-beta antibody attenuated the effect of gp160-MSP
       on MC proliferation at lower as well as higher concentrations.
       Bromodeoxyuridine incorporation studies also showed the modulation of MC
       proliferation by gp160-MSP. Interaction of other HIV proteins such as
       HIV-1 Gag4 and HIV-1 Tat with macrophages did not affect MC
       proliferation when compared with MSP alone. gp160-MSP also enhanced (P <
       0.001) synthesis of type IV collagen by MC (control, 467.8 +/- 9.0; MSP,
       501.0 +/- 25.0; gp160-MSP, 775.5 +/- 39.0 ng/mg protein). The effect of
       gp160-MSP on collagen synthesis by MC was dose-dependent. Anti-TGF-beta
       antibody attenuated the gp160-MSP-induced mesangial cell collagen
       synthesis. The present study provides a basis for speculation that
       macrophage-gp160 interaction products have the potential to cause
       expansion of the mesangium.
 DE    Animal  Antibodies, Monoclonal/IMMUNOLOGY  Cell Division/DRUG EFFECTS
       Cell Line  Culture Media, Conditioned/PHARMACOLOGY  Extracellular
       Matrix/*DRUG EFFECTS/SECRETION  Gene Products, env/*PHARMACOLOGY  Gene
       Products, gag/PHYSIOLOGY  Gene Products, tat/PHYSIOLOGY  Glomerular
       Mesangium/*CYTOLOGY/*METABOLISM  Human  Leukocytes, Mononuclear/DRUG
       EFFECTS/PHYSIOLOGY  Lymphoma, Large-Cell/CHEMISTRY  Macrophages/DRUG
       EFFECTS/*PHYSIOLOGY  Mice  Protein Precursors/*PHARMACOLOGY  Support,
       U.S. Gov't, P.H.S.  Transforming Growth Factor beta/IMMUNOLOGY/SECRETION
       Tumor Cells, Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

