Transfused Macrophages Ameliorate Pancreatic and Renal Injury in Murine Diabetes Mellitus (original) (raw)
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Review Articles| February 11 2011
aCentre for Transplant and Renal Research, University of Sydney, Westmead Millennium Institute, and bCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, N.S.W., Australia
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aCentre for Transplant and Renal Research, University of Sydney, Westmead Millennium Institute, and bCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, N.S.W., Australia
Search for other works by this author on:
aCentre for Transplant and Renal Research, University of Sydney, Westmead Millennium Institute, and bCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, N.S.W., Australia
Search for other works by this author on:
aCentre for Transplant and Renal Research, University of Sydney, Westmead Millennium Institute, and bCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, N.S.W., Australia
Search for other works by this author on:
aCentre for Transplant and Renal Research, University of Sydney, Westmead Millennium Institute, and bCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, N.S.W., Australia
Search for other works by this author on:
aCentre for Transplant and Renal Research, University of Sydney, Westmead Millennium Institute, and bCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, N.S.W., Australia
Search for other works by this author on:
aCentre for Transplant and Renal Research, University of Sydney, Westmead Millennium Institute, and bCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, N.S.W., Australia
Search for other works by this author on:
aCentre for Transplant and Renal Research, University of Sydney, Westmead Millennium Institute, and bCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, N.S.W., Australia
Search for other works by this author on:
aCentre for Transplant and Renal Research, University of Sydney, Westmead Millennium Institute, and bCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, N.S.W., Australia
Search for other works by this author on:
aCentre for Transplant and Renal Research, University of Sydney, Westmead Millennium Institute, and bCentre for Kidney Research, Children’s Hospital at Westmead, Sydney, N.S.W., Australia
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Nephron Experimental Nephrology (2011) 118 (4): e87–e99.
Abstract
Background: Alternatively activated macrophages (M2 macrophages) are able to reduce renal injury in murine adriamycin nephropathy. However, the effect of M2 macrophages in other renal diseases such as diabetic nephropathy remains unknown. Methods: Macrophages were separated from splenocytes and polarized with IL-4 and IL-13 into a protective phenotype. Mice underwent adoptive transfer with M2 macrophages, and then diabetes was induced by tail vein injection with streptozotocin (STZ). Blood glucose levels were monitored daily. Mice were sacrificed at week 10 after STZ. Renal function and histopathological injury were assessed quantitatively. Results: Transfused M2 macrophages accumulated progressively in kidneys for up to 10 weeks after STZ. Kidneys from diabetic mice transfused with M2 macrophages had less tubular atrophy, glomerular hypertrophy and interstitial expansion than did control diabetic mice. M2 macrophages suppressed the development of interstitial fibrosis. In addition, the degree of pancreatic islet injury, as assessed by insulin staining, haemoglobin A1c and blood glucose was reduced after transfusion of M2 macrophages. In vivo, activation of kidney endogenous macrophage cytokine expression was inhibited by M2 macrophages. Conclusion: Our findings show that M2 macrophages can protect against islet and renal injury in streptozotocin-induced diabetes, providing a potential therapeutic strategy for diabetes and diabetic nephropathy.
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