Constitutive production of regulators of stem cell proliferation in the hereditarily anaemic belgrade laboratory (b/b) rat

The Belgrade (b/b) rat has hereditary hypochromic microcytic anaemia as the consequence of intracellular iron deficiency together with decreased number and proliferative activity (a proliferative block) of progenitors and more mature stem cells (CFU-Sd8). In the present study, the investigations were extended to the activities influencing CFU-S proliferation in bone marrow of b/b rats. A stimulator of CFU-S proliferation (not associated with IL-1 and IL-6 activity), undetectable in steady-state haematopoiesis in bone marrow, was found in b/b rat. The inhibitor of CFU-S proliferation, present in the bone marrow of normal animals, was also detected in b/b rats, indicating impaired synchronisation of production of two opposite activities. The chronic treatment of b/b rats with iron increased proliferative activity of CFU-S, corrected anaemia whilst, only the activity of stimulator was detected indicating recovery of synchronisation in stimulator and inhibitor production. Complete correction of anaemia by chronic RBC transfusions of b/b rats normalised production of CFU-S proliferation regulators. Disturbances in production of regulators of CFU-S proliferation may result as a secondary consequence of the metabolic alterations associated with severe anaemia.