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Graft, Vol. 5, No. 3, 141-144 (2002)
DOI: 10.1177/1522162802005003005
© 2002 SAGE Publications

Sequential Activation Patterns of Macrophages in Chronic Allograft Nephropathy

Erwei Song

Balazs Antus

Yousheng Yao

Jens Lutz

Uwe Heemann

Infiltration of macrophages is associated with the development of chronic allograftnephropathy. Macrophages can be activated in a classical pathway characterized byTNF-{alpha} expression, and an alternative pathway characterized by the expression of alter-nativemacrophage activation-associated CC-chemokine-1 (AMAC-1). The presentstudy investigated the sequential activation patterns of macrophages in the course ofchronic allograft nephropathy. Fisher (F344) rat kidneys were orthotopically transplantedinto Lewis recipients and harvested at week 1, 2, 12, 16, 20, 24, or 28 after transplantationfor histologic, immunohistologic, and molecular analysis. TNF-{alpha} mRNA waselevated at weeks 1 and 2 following transplantation, and could not be detected at latestages, whereas AMAC-1 mRNA began to be detectable at 12 weeks and increasedsteadily thereafter. Furthermore, AMAC-1 mRNA levels positively correlated with urinaryprotein excretion ( r = 0.685, P< 0.05), and glomerulosclerosis ( r = 0.725, P< 0.05) atthe end of the follow-up. Hence, infiltrating macrophages are classically activated earlyand, alternatively, late after transplantation. Alternatively activated macrophages maybe responsible for chronic allograft nephropathy.

Key Words: kidney transplantation • chronic rejection • macrophage • classical activation • alternative activation


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