MIP-1-ALPHA INCREASES THE SELF-RENEWAL CAPACITY OF THE HEMATOPOIETIC SPLEEN-COLONY-FORMING CELLS FOLLOWING HYDROXYUREA TREATMENT IN-VIVO

In this report, the effect of macrophage inflammatory protein (MIP-1 a lpha) on the self-renewal, in vivo, of haemopoietic spleen colony-form ing units (CFU-S) following cytotoxic damage, has been investigated. C FU-S recovery following injection of hydroxyurea, HU (1 g/kg at O and 7 hrs) with or without MIP-1 alpha intervention was measured over the following 5 days. In addition to the initial protection conferred by M IP-1 alpha, the CFU-S population recovered about 1.7 times faster than in the unprotected controls. Direct measurement of the self-renewal c apacity of the CFU-S population was made at 2 days after HU + MIP-1 al pha treatment by measuring the number of CFU-S/spleen colony in a seco ndary transplant assay. CFU-S following HU treatment alone generated 6 0 CFU-S/colony. Additional MIP-1 alpha treatment increased this to 90 CFU-S/colony. It is concluded that MIP-1 alpha modifies the generation age structure of a regenerating CFU-S population such that recovery i s initiated from the more primitive cells of the population's age spec trum and that this observation should extend the range of cytotoxic ag ents from which MIP-1 alpha can give protection.