Quantification and localization of M2 macrophages in human kidneys with acute tubular injury

This study addresses for the first time the question whether there is significant macrophage population in human kidney sections from patients with acute tubular injury (ATI). We examined therefore the interstitial macrophage population in human kidney tissue with biopsy-proven diagnosis of ATI, minimal change disease (MCD), and MCD with ATI. Kidney biopsies from patients with the above diagnoses were stained with antibodies directed against CD68 (general macrophage marker), CD163 (M2 marker), and HLA-DR (M1 marker) and their respective electron microscopy samples were evaluated for the presence of interstitial macrophages. Our study shows that patients with ATI have significantly increased numbers of interstitial CD68(+) macrophages, with an increase in both HLA-DR(+) M1 macrophages and CD163(+) M2 macrophages as compared to patients with MCD alone. Approximately 75% of macrophages were M2 (CD163(+)) whereas only 25% were M1 (HLA-DR(+)). M2 macrophages, which are believed to be critical for wound healing, were found to localize close to the tubular basement membrane of injured proximal tubule cells. Ultra structural examination showed close adherence of macrophages to the basement membrane of injured tubular epithelial cells. We conclude that macrophages accumulate around injured tubules following ATI and exhibit predominantly an M2 phenotype. We further speculate that macrophage-mediated repair may involve physical contact between the M2 macrophage and the injured tubular epithelial cell.