[HTML][HTML] Macrophage growth factors introduced into the kidney initiate renal injury
T Naito, H Yokoyama, KJ Moore, G Dranoff… - Molecular …, 1996 - Springer
T Naito, H Yokoyama, KJ Moore, G Dranoff, RC Mulligan, VR Kelley
Molecular Medicine, 1996•SpringerBackground CSF-1 expression precedes renal injury in autoimmune MRL-lpr mice and is
responsible for macrophage (Mϕ) proliferation and survival in the kidney. By comparison,
C3H-lpr mice do not express CSF-1 in the kidney, and despite the lpr mutation, kidneys
remain normal. The purpose of this study was to test the capacity of local and systemic
expression of Mϕ growth factor, CSF-1 to initiate renal injury in normal (C3H-++, MRL-++)
and autoimmune (C3H-lpr, MRL-lpr) mice. Materials and Methods We designed a gene …
responsible for macrophage (Mϕ) proliferation and survival in the kidney. By comparison,
C3H-lpr mice do not express CSF-1 in the kidney, and despite the lpr mutation, kidneys
remain normal. The purpose of this study was to test the capacity of local and systemic
expression of Mϕ growth factor, CSF-1 to initiate renal injury in normal (C3H-++, MRL-++)
and autoimmune (C3H-lpr, MRL-lpr) mice. Materials and Methods We designed a gene …
Background
CSF-1 expression precedes renal injury in autoimmune MRL-lpr mice and is responsible for macrophage (Mϕ) proliferation and survival in the kidney. By comparison, C3H-lpr mice do not express CSF-1 in the kidney, and despite the lpr mutation, kidneys remain normal. The purpose of this study was to test the capacity of local and systemic expression of Mϕ growth factor, CSF-1 to initiate renal injury in normal (C3H-++, MRL-++) and autoimmune (C3H-lpr, MRL-lpr) mice.
Materials and Methods
We designed a gene transfer system to deliver cytokines into the kidney by transducing renal tubular epithelial cells (TEC) using retroviral vectors expressing CSF-1 or another Mϕ growth factor, GM-CSF. We placed transduced syngeneic cytokine-TEC under the renal capsule of normal and autoimmune prone mice prior to renal injury and evaluated renal pathology at 3, 7, 14, 28, and 90 days postimplant.
Results
CSF-1-TEC and GM-CSF-TEC, but not uninfected TEC, caused extensive local renal injury in strains with the lpr mutation. At 3–7 days the infiltrating cells were mainly Mϕ, and by 28 days they were predominantly lymphocytes. By comparison, the kidneys of MRL-++ and C3H-++ mice remained normal. Implanted genetically modified TEC caused a sustained increase of CSF-1 or GM-CSF in the circulation which did not modify the contralateral kidney.
Conclusions
Gene transfer of Mϕ growth factors into the kidney initiates severe local renal injury in autoimmune prone mice with the lpr mutation, but does not compromise the kidney in nonautoimmune hosts. Of note, introduction of Mϕ growth factors into the kidney of C3H-lpr mice which do not spontaneously develop renal injury incites renal damage. These studies offer a gene transfer approach to explore the impact of local and systemic cytokine production on renal injury.
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