Molecular basis of the recognition of intravenously transplanted hemopoietic cells by bone marrow

Abstract

Bone marrow transplantation is done by introducing a source of hemopoietic stem cells into general circulation in anticipation of their recognition and selective lodging into the bone marrow. We tested the hypothesis that the molecular basis of this recognition is by means of a lectin-carbohydrate interaction. We synthesized a number of neoglycoproteins by covalently binding pyranose derivatives of various monosaccharides to bovine serum albumin (BSA). These reagents and the galactosyl-terminating glycoprotein asialofetuin were used to inhibit engraftment of intravenously transplanted marrow cells into lethally irradiated mice. In splenectomized mice, in whom engraftment occurs only in the bone marrow, galactosyl-BSA, mannosyl-BSA, and asialofetuin but not fucosyl-BSA inhibited homing of transplanted cells. Both the survival and cellular content of marrow, including hemopoietic stem cells and granulocyte-macrophage progenitors, were reduced. In nonsplenectomized mice, in whom engraftment occurs in both spleen and marrow, the reagents did not inhibit splenic homing. Both the survival and cellular content of spleen, including hemopoietic stem cells and granulocyte-macrophage progenitors, were similar to those of the control group. But even in this group, marrow homing of transplanted cells was inhibited by these reagents. We conclude that the recognition and homing of intravenously transplanted hemopoietic cells by marrow, but not by spleen, occurs by means of a recognition system with galactosyl and mannosyl specificities.