MIP-1 alpha increases the self-renewal capacity of the hemopoietic spleen-colony-forming cells following hydroxyurea treatment in vivo.

Abstract

In this report, the effect of macrophage inflammatory protein (MIP-1alpha) on the self-renewal, in vivo, of haemopoietic spleen colony-forming units (CFU-S) following cytotoxic damage, has been investigated. CFU-S recovery following injection of hydroxyurea, HU (1 g/kg at 0 and 7 hers) with or without MIP-1alpha intervention was measured over the following 5 days. In addition to the initial protection conferred by MIP-1alpha, the CFU-S population recovered about 1.7 times faster than in the unprotected controls. Direct measurement of the self-renewal capacity of the CFU-S population was made at 2 days after HU + MIP-1alpha treatment by measuring the number of CFU-S/spleen colony in a secondary transplant assay. CFU-S following HU treatment alone generated 60 CFU-S/colony. Additional MIP-1alpha treatment increased this to 90 CFU-S/colony. It is concluded that MIP-1alpha modifies the generation age structure of a regenerating CFU-S population such that recovery is initiated from the more primitive cells of the population's age spectrum and that this observation should extend the range of cytotoxic agents from which MIP-1alpha can give protection.