Original Article

Pediatric Nephrology

, Volume 20, Issue 12, pp 1708-1716

First online:

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

  • Pingtao TangAffiliated withCenter for Genetic Medicine, Children’s Research Institute, Children’s National Medical Center
  • , Marina JerebtsovaAffiliated withCenter for Genetic Medicine, Children’s Research Institute, Children’s National Medical CenterDepartment of Pediatrics, The George Washington University
  • , Ronald PrzygodzkiAffiliated withCenter for Genetic Medicine, Children’s Research Institute, Children’s National Medical CenterDivision of Pathology, Children’s National Medical CenterDepartment of Pediatrics, The George Washington University
  • , Patricio E. RayAffiliated withCenter for Genetic Medicine, Children’s Research Institute, Children’s National Medical CenterDivision of Nephrology, Children’s National Medical CenterDepartment of Pediatrics, The George Washington University Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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 α5 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 (5×108 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.

Keywords

Fibroblast growth factor-2 (FGF-2) Renal tubular epithelial cells Attachment HIV-1 nephropathy HIV-infected mononuclear cells Renal disease