EFFECT OF ASIALOFETUIN ON PROLONGATION OF SKIN ALLOGRAFT SURVIVAL BY DONOR BONE-MARROW CELLS

Survival of skin allografts made to antilymphocyte serum (ALS)-treated recipients is prolonged by posttransplant intravenous injection of do nor strain bone marrow cells (BMC). If asialofetuin (ASF) is coinjecte d with the BMC, the prolonged graft survival is augmented (e.g., media n survival time increased from 43 days to 72 days by injection of ASF) . We have confirmed that, like peanut agglutinin-binding stem cells, t he active BMC are at risk for hepatic sequestration after injection, p ossibly via hepatic asialoglycoprotein receptors. A fraction enriched for these active cells binds to liver sections in vitro and localizes to Liver in vivo. This binding and localization can be partly inhibite d by ASF. Although injected cells could also be found in the spleen, t he beneficial effect of ASF could be demonstrated in previously splene ctomized mice. Also, splenectomy 2 hr after BMC injection (without ASF ) had little effect on the BMC-induced prolonged graft survival, while transfer of cells from the removed spleens to secondary ALS-treated r ecipients did not transfer such prolongation. In contrast, transfer of BMC from primary, donor marrow-injected recipients did transfer graft -prolonging activity, especially if both primary and secondary recipie nts were ASF injected. Our results suggest that recipient marrow, but not spleen, is the site of short-term localization of graft survival-p rolonging BMC. Augmentation of allograft survival with ASF in AI;S-tre ated recipients appears to result from the diversion of BMC away from a microenvironment not conducive to the expression of their graft-prol onging activity.