DIFFERENTIAL SURFACE EXPRESSION OF CELL-ADHESION MOLECULES DURING GRANULOCYTE MATURATION

Individual steps of granulocyte maturation, such as lineage commitment , proliferation, maturation, and migration from the marrow to the peri pheral blood, may be influenced by distinct interactions with the bone marrow stroma. To identify candidates of membrane components involved in maturational stage-specific interactions, we studied changes in th e expression of cell adhesion molecules along the granulocyte maturati onal pathway. Three-color flow cytometric measurements were used to me asure levels of cell adhesion molecules along this pathway. The alpha chains of VLA-4 (CD49d) and VLA-5, the integrin beta1 chain (CD29), an d CD31 (PECAM-1) were expressed in high density on all early myeloid c ells but down-modulated during postproliferative maturation. CD44 and L-selectin were expressed on CD34+ myeloid progenitor cells and mature granulocytes but down-modulated during the intermediate stages of mat uration. The granulocyte receptor for endothelial selectins, sLe(x), w as specifically expressed by myeloid progenitor cells. sLe(x) was down -modulated during the intermediate stages of granulocyte maturation bu t up-regulated again during terminal maturation. In contrast, CD67, a putative granulocyte adhesion molecule, was negative on progenitors, t ransiently up-regulated during the intermediate stages of maturation, and almost absent from the surface of mature granulocytes. These resul ts show that each stage of granulocyte maturation is associated with t he expression of a unique combination of cell adhesion molecules. L-se lectin, CD44, and beta1 integrins were regulated as previously describ ed for immature lymphopoietic cells and may therefore play general rol es in the compartmentalization and development of leukocytes. In contr ast, sLe(x) and CD67 were specifically expressed by myeloid cells and could be specifically important for compartmentalization of distinct p hases of granulocyte maturation.