Improved longevity of hematopoiesis in long-term bone marrow cultures and reduced irradiation-induced pulmonary fibrosis in Toll-like receptor-4 deletion recombinant-negative mice.

Abstract

AIM: We measured long-term hematopoiesis in continuous bone marrow cultures derived from Toll-like receptor-4 (Tlr4(-/-))(C57BL/6J) mice. MATERIALS AND METHODS: We measured hematopoiesis in vitro over 27 weeks in long-term bone marrow cultures from Tlr4(-/-) and control mice, and irradiation-induced pulmonary fibrosis in mice irradiated to 20 Gy to the thorax. RESULTS: There was a significant increase in the duration of hematopoiesis in long-term bone marrow cultures from Tlr4(-/-) mice in production of total non-adherent cells and day 7 and day 14 multi-lineage colony-forming cells. The histology of bone marrow hematopoietic and stromal cell lines was indistinguishable between different mouse strains. There was no detectable late irradiation pulmonary fibrosis in Tlr4(-/-) mice. CONCLUSION: Homozygous deletion of both alleles of Tlr4, encoding for an inflammatory mediator receptor, improves the duration of hematopoiesis in vitro and reduces irradiation-induced lung fibrosis.