Fibroblast growth factor-2 increases the renal recruitment and attachment of HIV-infected mononuclear cells to renal tubular epithelial cells.
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.
Tang
Pingtao
P
Center for Genetic Medicine, Children's Research Institute, Children's National Medical Center, Washington, DC, 20010, USA.
Jerebtsova
Marina
M
Przygodzki
Ronald
R
Ray
Patricio E
PE
D016263:AIDS-Associated Nephropathy / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002648:Child; D018920:Coculture Techniques; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000821:virology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism; D005822:Genetic Vectors; D015658:HIV Infections / Q000097:blood / Q000652:urine; D015497:HIV-1; D006801:Humans; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000166:cytology* / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects* / Q000821:virology; D011994:Recombinant Proteins / Q000494:pharmacology
D004279:DNA, Viral; D005353:Fibronectins; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2