Cellular injury associated with renal thrombotic microangiopathy in human immunodeficiency virus-infected macaques.
Pigtailed macaques infected with a virulent human immunodeficiency virus-2 (HIV-2) strain develop renal thrombotic microangiopathy (TMA), which morphologically resembles aspects of human HIV-associated TMA. Apoptotic cell death of microvascular endothelial cells might be a pathogenetic clue to this disease. For defining further the pattern of cellular injury in this model, serial kidney sections of 58 macaques infected with HIV-2 and 7 uninfected controls were studied by routine microscopy, terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL), 4',6-diamidino-2-phenylindole staining, and immunohistochemistry for single-stranded DNA, p53, the Wilms' tumor suppressor gene-1 peptide product, caspase-3, and the proliferation marker Ki67. Selected cases were further evaluated by in situ end labeling and transmission electron microscopy. Kidneys of 13 HIV-2-infected animals contained a pattern of cellular injury, which was characterized by (1) nuclear swelling with an ultrastructural morphology different from apoptotic nuclei, (2) sharply demarcated areas of renal cells with chromatin nicks (TUNEL positive) and single-stranded DNA, (3) absence of an inflammatory or proliferative response, (4) upregulation of p53 and loss of at least one cellular differentiation marker (Wilms' tumor suppressor gene-1), (5) a tight correlation with the diagnosis of renal TMA, and (6) a contrast between profound changes in the renal cellular morphology and the apparently unaffected clinical condition of the host. This pattern of injury, which shares some features of both apoptotic and oncotic necrosis, might be involved in the pathogenesis of HIV-associated renal TMA in this model.
Segerer
Stephan
S
*Department of Pathology, University of Washington, Seattle, Washington; and Division of Nephrology, University of Aachen, Aachen, Germany.
Eitner
Frank
F
*Department of Pathology, University of Washington, Seattle, Washington; and Division of Nephrology, University of Aachen, Aachen, Germany.
Cui
Yan
Y
*Department of Pathology, University of Washington, Seattle, Washington; and Division of Nephrology, University of Aachen, Aachen, Germany.
Hudkins
Kelly L
KL
*Department of Pathology, University of Washington, Seattle, Washington; and Division of Nephrology, University of Aachen, Aachen, Germany.
Alpers
Charles E
CE
*Department of Pathology, University of Washington, Seattle, Washington; and Division of Nephrology, University of Aachen, Aachen, Germany.
D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000648:ultrastructure; D015658:HIV Infections / Q000150:complications*; D015498:HIV-2; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000473:pathology; D008251:Macaca; D008833:Microcirculation; D009336:Necrosis; D012079:Renal Circulation; D013927:Thrombosis / Q000150:complications* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025721:WT1 Proteins / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins