Abstract
BackgroundCD18 is the common beta subunit of β2 integrins, which are expressed on hematopoietic cells. β2 integrins are essential for cell adhesion and leukocyte trafficking.MethodsHere we have analyzed the expression of CD18 in different subsets of human hematopoietic stem and progenitor cells (HSPCs) from cord blood (CB), bone marrow (BM), and mobilized peripheral blood (mPB) samples. CD34+ cells were classified into CD18high and CD18low/neg, and each of these populations was analyzed for the expression of HSPC markers, as well as for their clonogenity, quiescence state, and repopulating ability in immunodeficient mice.ResultsA downregulated membrane expression of CD18 was associated with a primitive hematopoietic stem cells (HSC) phenotype, as well as with a higher content of quiescent cells and multipotent colony-forming cells (CFCs). Although no differences in the short-term repopulating potential of CD18low/neg CD34+ and CD18high CD34+ cells were observed, CD18low/neg CD34+ cells were characterized by an enhanced long-term repopulating ability in NSG mice.ConclusionsOverall, our results indicate that the downregulated membrane expression of CD18 characterizes a primitive population of human hematopoietic repopulating cells.
Highlights
CD18 is the common beta subunit of β2 integrins, which are expressed on hematopoietic cells. β2 integrins are essential for cell adhesion and leukocyte trafficking
Evident increases in primitive populations were observed in the CD18low/neg fraction when other Hematopoietic stem cells (HSCs) markers were considered
The proportion of very primitive CD34+CD38−CD45RA−CD90+ HSCs was 23 times higher in the CD18low/neg population as compared to the CD18high population (7 × 10−3% vs 4 × 10−4%, respectively) (Fig. 1a), confirming that the reduced expression of CD18 was associated with an increased proportion in cells with a primitive HSC phenotype
Summary
CD18 is the common beta subunit of β2 integrins, which are expressed on hematopoietic cells. β2 integrins are essential for cell adhesion and leukocyte trafficking. CD18 is the common beta subunit of β2 integrins, which are expressed on hematopoietic cells. All leukocytes express the lymphocyte function-associated antigen 1 (LFA-1) on their surface. Macrophage 1 antigen (Mac-1) is mostly expressed in the myeloid lineage, where it mediates a range of functions such as phagocytosis, degradation, and remodeling of the extracellular matrix. Integrin p150.95 is expressed in myeloid cells, dendritic cells, NK cells, and populations of activated T and B cells. It mediates phagocytosis of inactive complement component 3b (iC3b)-opsonized particles and it is involved in the adhesion of monocytes to endothelial cells. Integrin αDβ2 is expressed at a basal level on the surface of most leukocytes and is upregulated on phagocytic leukocytes present in regions of local inflammation, its specific role in leukocyte function remains unknown [3]
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