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1996-02-27
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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).