Fibroblast growth factor-2 increases the renal recruitment and attachment of HIV-infected mononuclear cells to renal tubular epithelial cells

Pediatr Nephrol. 2005 Dec;20(12):1708-16. doi: 10.1007/s00467-005-2018-2. Epub 2005 Aug 16.

Abstract

The role of circulating growth factors in the pathogenesis of childhood HIV-1-associated nephropathy (HIVAN) is not clearly understood. In previous studies, we found a significant accumulation of fibroblast growth factor-2 (FGF-2) in the circulation and kidneys of children with HIVAN. The purpose of this study was to determine whether circulating FGF-2 may play a role in the pathogenesis of HIVAN by increasing the renal recruitment and attachment of HIV-infected mononuclear cells to renal epithelial cells. Using in vitro cell adhesion assays, we showed that FGF-2 increased the attachment of peripheral blood mononuclear cells (PBMCs) to fibronectin-coated tissue culture dishes by approximately threefold through a mechanism that involved the alpha5 integrin subunit. In addition, we found that FGF-2 induces a similar increase in the attachment of HIV-infected PBMCs and monocytes/macrophages to plastic tissue culture dishes and to monolayers of primary renal tubular epithelial cells harvested from the urine of HIV-infected children with renal disease. Finally, we injected 16 adult C57Bl6/J male mice with recombinant adenoviral vectors carrying either the LacZ gene or a secreted form of human FGF-2 (5 x 10(8)pfu/mouse) and demonstrated that high levels of circulating FGF-2 can increase the renal recruitment of circulating inflammatory cells and induce transient tubulointerstitial injury in vivo. These data suggest that FGF-2 may have an immunomodulatory role in the pathogenesis of HIVAN by recruiting HIV-infected cells in the kidney.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Associated Nephropathy / pathology
  • AIDS-Associated Nephropathy / physiopathology*
  • AIDS-Associated Nephropathy / virology
  • Adenoviridae / genetics
  • Animals
  • Cell Adhesion
  • Cell Culture Techniques
  • Cells, Cultured
  • Child
  • Coculture Techniques
  • DNA, Viral / genetics
  • DNA, Viral / isolation & purification
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / drug effects*
  • Epithelial Cells / virology
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibronectins / metabolism
  • Genetic Vectors
  • HIV Infections* / blood
  • HIV Infections* / urine
  • HIV-1*
  • Humans
  • Immunohistochemistry
  • Kidney Tubules / cytology*
  • Kidney Tubules / virology
  • Macrophages / drug effects
  • Macrophages / virology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / drug effects*
  • Monocytes / virology
  • Recombinant Proteins / pharmacology

Substances

  • DNA, Viral
  • Fibronectins
  • Recombinant Proteins
  • Fibroblast Growth Factor 2