Figure 1.

Inflammatory leukocyte infiltrates are present in rejected human allografts. (A) Schematic diagram illustrating our working model. In response to ischemic kidney injury or inflammation upon allograft transplantation, CD11b+ leukocytes are recruited into the tissue, where they induce an adaptive response and further recruitment of innate and adaptive immune cells. Increased inflammation results in progressive tissue damage, nephropathy and, eventually, graft failure. Given that CD11b+ leukocyte infiltration into the allograft is an early event, blocking influx of these innate immune cells via novel small molecule CD11b agonists is expected to reduce inflammation, decrease progressive tissue damage and prolong allograft survival. (B) Representative micrographs of human kidney tissue sections (from a healthy cadaveric donor or a rejected allograft) after histochemical and immunofluorescence analyses. Sequential sections from each tissue were stained with periodic acid-Schiff (PAS) or trichrome and imaged using light microscopy. Sections were also stained with antibodies specific for CD45, CD11b, or CD3, as indicated, followed by fluorescently labeled secondary antibodies and then imaged using a confocal microscope. The rejected allograft shows enhanced trichrome staining (indicating an increase in interstitial fibrosis) and increased numbers of CD45+, CD11b+, and CD3+ immune cells as compared to the healthy kidney (n = 4–5/group). Scale bar = 50 μm.