Extra-hepatic derivation of Kupffer cells during oestrogenic stimulation of parabiosed mice

Abstract

(CBA × CBA-T6T6)F₁ mice were given 850 r whole body irradiation and “repopulated” with CBA-T6T6 bone marrow and CBA lymph node cells. Macrophages were isolated from the liver 2 weeks later, following stimulation with 5 daily injections of diethylstilboestrol and analysed karyotypically. The majority of dividing cells were donor-derived, and predominantly of bone marrow ancestry. The phagocytic identity of these proliferating cells was established by the association of ingested Thorotrast with metaphases and with cells labelled by ³H-thymidine incorporation.

Similar evidence for extra-hepatic derivation of a substantial number of dividing liver macrophages without prior irradiation was obtained when diethylstilboestrol was administered to CBA and CBA-T6T6 mice separated after 1 week to 5 months of parabiosis. Partner-derived mitoses were found in all animals studied, varying between 4 and 29 per cent. Reciprocal colonisation in the liver was greater when oestrogenic stimulation was applied during parabiosis and near-equilibrium was found after 6 months union. The association of phagocytosed particles with ³H-thymidine labelling or mitoses confirmed the functional identity of these cells.

It is proposed that normal Kupffer cells are not a separate self-replicating population of phagocytes, but rather can be replaced and augmented by haematogenous recruitment of the same precursor in bone marrow as are “free” macrophages.