Background: The collagen receptor glycoprotein VI generates activating signals through an immunoreceptor tyrosine-based activating motif on the co-associated Fc receptor gamma chain. Leukocyte-associated immunoglobulin-like receptor-1 also ligates collagen but generates inhibitory signals through immunoreceptor tyrosine-based inhibitory motifs. Thus far, the cellular expression of glycoprotein VI and leukocyte-associated immunoglobulin-like receptor-1 appears mutually exclusive.
Design and methods: Using flow cytometry, we studied expression of collagen receptors on differentiating human megakaryocytes. CD34(+) cells were isolated from umbilical cord blood and matured to megakaryocytes in vitro. Freshly isolated bone marrow cells were used to study primary megakaryocytes. Upon cell sorting, cytospins were made to examine cytological characteristics of differentiation.
Results: Megakaryocyte maturation is accompanied by up-regulation of glycoprotein VI and down-regulation of leukocyte-associated immunoglobulin-like receptor-1. Interestingly, both in cultures from hematopoietic stem cells and primary cells obtained directly from bone marrow, we identified a subset of morphologically distinct megakaryocytes which co-express glycoprotein VI and leukocyte-associated immunoglobulin-like receptor-1.
Conclusions: This is the first report of a primary cell that co-expresses these collagen receptors with opposite signaling properties. Since megakaryocytes mature in the collagen-rich environment of the bone marrow, these findings may point to a role for leukocyte-associated immunoglobulin-like receptor-1 in the control of megakaryocyte maturation/migration.