Pediatric Nephrology

, Volume 20, Issue 12, pp 1708–1716

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

Authors

  • Pingtao Tang
    • Center for Genetic Medicine, Children’s Research InstituteChildren’s National Medical Center
  • Marina Jerebtsova
    • Center for Genetic Medicine, Children’s Research InstituteChildren’s National Medical Center
    • Department of PediatricsThe George Washington University
  • Ronald Przygodzki
    • Center for Genetic Medicine, Children’s Research InstituteChildren’s National Medical Center
    • Division of PathologyChildren’s National Medical Center
    • Department of PediatricsThe George Washington University
    • Center for Genetic Medicine, Children’s Research InstituteChildren’s National Medical Center
    • Division of NephrologyChildren’s National Medical Center
    • Department of PediatricsThe George Washington University
Original Article

DOI: 10.1007/s00467-005-2018-2

Cite this article as:
Tang, P., Jerebtsova, M., Przygodzki, R. et al. Pediatr Nephrol (2005) 20: 1708. doi:10.1007/s00467-005-2018-2

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 cellsAttachmentHIV-1 nephropathyHIV-infected mononuclear cellsRenal disease

Copyright information

© IPNA 2005