High impact information on VNN2

• This novel GPI-anchored protein (GPI-80) is highly homologous with Vanin-1, a recently reported GPI-anchored protein that is expressed on perivascular thymic stromal cells and is involved in thymus homing in mice [1].
• GPI-80 is expressed mainly in human neutrophils [2].
• Expression of GPI-80, a beta2-integrin-associated glycosylphosphatidylinositol-anchored protein, requires neutrophil differentiation with dimethyl sulfoxide in HL-60 cells [2].
• GPI-80 is a member of the amidohydrolase family that has been proposed as a potential regulator of beta2-integrin-dependent leukocyte adhesion [2].
• Granulocyte colony-stimulating factor, which augments neutrophil differentiation of HL-60 cells, up-regulated GPI-80 expression in the presence of DMSO [2].

Biological context of VNN2

• However, it is not yet known how GPI-80 regulates cell adhesion and migration [3].
• These results suggest that almost all GPI-80 positive monocytes belong to a monocyte subpopulation that is superior in phagocytosis and reactive oxygen production, but inferior in antigen presentation [4].
• Glycosylphosphatidyl inositol-anchored protein (GPI-80) gene expression is correlated with human thymoma stage [5].
• Cross-linking of GPI-80, a possible regulatory molecule of cell adhesion, induces up-regulation of CD11b/CD18 expression on neutrophil surfaces and shedding of L-selectin [6].
• CD11b and GPI-80, reactive oxygen species (ROS) generation, changes in the cell cycle, and apoptosis were used as markers of differentiation [7].

Anatomical context of VNN2

• We report here the identification of two distinct human cDNAs, called VNN1 and VNN2, related to the recently described mouse Vanin-1 molecule involved in lymphocyte migration (M. Aurrand-Lions et al., 1996, Immunity 5: 391-405) [8].
• To verify this, we examined whether GPI-80 is expressed on the human promyelocytic leukemia cell line HL-60 following treatment with differentiation inducers [2].
• Thus, we identify secretory vesicles as the reservoir of GPI-80 from which it may translocate to the plasma membrane after weak stimulation of the cells [9].
• Increasing amounts of GPI-80 were exposed on the cell surface after weak stimulation with the chemoattractant fMLF, suggesting that the protein can be translocated to the plasma membrane from intracellular stores [9].
• In contrast, GPI-80 expression was low in HLA-DQ-positive monocytes [4].

Associations of VNN2 with chemical compounds

• Adhesion of DMSO-induced cells was regulated by anti-GPI-80 monoclonal antibody, similar to the regulation observed in neutrophils [2].
• On the other hand, all-trans-retinoic acid (ATRA), another neutrophil-inducing reagent, induced no clear GPI-80 expression [2].
• 1 GPI-80, a glycosylphosphatidylinositol (GPI)-anchored protein initially identified on human neutrophils, plays a role(s) in the regulation of beta2 integrin function [10].
• They also suggest that cytochalasin B, genistein, and SB203580 inhibit GPI-80 release by suppressing signals for cell adherence, rather than by a direct effect on its secretion [10].
• 3 Cytochalasin B, genistein, and SB203580 but not PD98059 inhibited TNF-alpha-stimulated GPI-80 release and neutrophil adherence at the same concentration [10].

Other interactions of VNN2

• On resting neutrophils, GPI-80 was evenly distributed on the cell surface and was associated with CD18 [3].
• Using anti-CD14 and anti-CD16 mAbs, almost all GPI-80-bearing monocytes belong to the strongly CD14-positive monocyte subpopulation [4].
• 4 Antioxidants (pyrrolidine dithiocarbamate and N-acetyl-L-cysteine) inhibited GPI-80 release by TNF-alpha stimulation, but superoxide dismutase did not [10].
• The distribution of GPI-80 on cell surfaces is similar to that of uPAR [3].
• GPI-80-positive cells were found in the well-differentiated CD11b-positive and transferrin-receptor-negative cell population [2].

Analytical, diagnostic and therapeutic context of VNN2

• In this study, we examined the precise distribution of GPI-80-positive monocytes using flow cytometry [4].
• Serum level of GPI-80 was confirmed to be elevated in stage IV thymoma compared with in stage I thymoma by using sandwich ELISA [5].
• In this study, we examined by immuno- and scanning electron microscopy, the distribution of GPI-80 on neutrophil surfaces [11].

References