Kupffer cells are absent in the livers of Hmox1^−/− animals and a human patient, but BMT restores Kupffer cells to Hmox1^−/− mice. (A) Immunohistochemistry for the pan-macrophage marker, F4/80, indicated that Kupffer cells were virtually absent in the livers of Hmox1^−/− sham mice (upper middle and right) in comparison with WT mice (left). F4/80-positive cells turned brown after diaminobenzidine staining (arrowheads). BMT completely restored macrophage populations in Hmox1^−/− animals (lower middle and right). Results are shown for Hmox1^−/− animals that were 4 months (middle) or 1.7 months (right) old at the time the BMT procedure was performed. (B) Expression of the marker of M2 polarized macrophages indicated that CD163 was partially restored in liver, BM, and spleen of KO BMT mice, as determined by quantitative reverse-transcription polymerase chain reaction. ND, not detected. (C) CD163 Kupffer cells normally found in human liver (left) were undetectable in the liver of an HMOX1-deficient patient (right). Scale bars represent 50 μm (A) and 25 μm (C).