Fast decline of hematopoiesis and uncoupling protein 2 content in human liver after birth: Location of the protein in Kupffer cells

Hepatic hematopoiesis is prominent during fetal life and ceases around birt h. In rodent liver, the decline of the hepatic hematopoiesis starts abruptl y at birth being accompanied by a decrease of mitochondrial uncoupling prot ein 2 (UCP2) expression in monocytes/macrophages. whereas hepatocytes may e xpress UCP2 only under pathologic situations. The goals of this study were to characterize hepatic hematopoiesis in humans around birth, and to identi fy cells expressing UCP2. Hematopoiesis was evaluated histologically in the liver of 22 newborns (mostly very premature neonates), who died between 45 min and 140 d after birth, and one fetus. UCP2 expression was characterize d by Northern blots, immunoblotting, immunohistochemistry, and by in situ h ybridization. The number of hematopoietic cells started to decrease rapidly at birth, irrespectively of the gestational age (23-40 wk) of neonates. A similar decline was observed for UCP2 expression, which was relatively high in fetal liver. UCP2 was detected only in myeloid cells (mainly in Kupffer cells), but not in hepatocytes. although sepsis or other pathologies occur red in the critically ill newborns. Kupffer cells represent the major site of mitochondrial UCP2 expression in the human newborn. UCP2 may be essentia l for the differentiation and function of macrophages and serve as a marker for these cells in human liver during the perinatal period.