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 donor strain bone marrow cells (BMC). If asialofetuin (ASF) is coinjected with the BMC, the prolonged graft survival is augmented (e.g., median survival time increased from 43 days to 72 days by injection of ASF). We have confirmed that, like peanut agglutinin-binding stem cells, the active BMC are at risk for hepatic sequestration after injection, possibly 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 inhibited by ASF. Although injected cells could also be found in the spleen, the beneficial effect of ASF could be demonstrated in previously splenectomized 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 recipients 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 recipients were ASF injected. Our results suggest that recipient marrow, but not spleen, is the site of short-term localization of graft survival-prolonging BMC. Augmentation of allograft survival with ASF in ALS-treated recipients appears to result from the diversion of BMC away from a microenvironment not conducive to the expression of their graft-prolonging activity.
Khouri
W
W
Department of Medical Laboratory Science, Bouvé College of Pharmacy and Health Sciences, Northeastern University, Boston, Massachusetts 02115.
Masli
S
S
De Fazio
S R
SR
Gozzo
J J
JJ
D000818:Animals; D001212:Asialoglycoproteins / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D060748:Fetuins; D006085:Graft Survival / Q000187:drug effects; D016219:Immunotherapy, Adoptive; D037102:Lectins / Q000494:pharmacology; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D019887:Peanut Agglutinin; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000494:pharmacology*
D001212:Asialoglycoproteins; D060748:Fetuins; D037102:Lectins; D019887:Peanut Agglutinin; D000509:alpha-Fetoproteins; C017029:asialofetuin