Infiltration of macrophages is associated with the development of chronic allograft nephropathy. Macrophages can be activated in a classical pathway characterized by TNF-α expression, and an alternative pathway characterized by the expression of alternative macrophage activation-associated CC-chemokine-1 (AMAC-1). The present study investigated the sequential activation patterns of macrophages in the course of chronic allograft nephropathy. Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients and harvested at week 1, 2, 12, 16, 20, 24, or 28 after transplantation for histologic, immunohistologic, and molecular analysis. TNF-α mRNA was elevated at weeks 1 and 2 following transplantation, and could not be detected at late stages, whereas AMAC-1 mRNA began to be detectable at 12 weeks and increased steadily thereafter. Furthermore, AMAC-1 mRNA levels positively correlated with urinary protein excretion (r = 0.685, P < 0.05), and glomerulosclerosis (r = 0.725, P < 0.05) at the end of the follow-up. Hence, infiltrating macrophages are classically activated early and, alternatively, late after transplantation. Alternatively activated macrophages may be responsible for chronic allograft nephropathy.
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