RESUMO
Selectins are carbohydrate-binding adhesion molecules that play important roles in control of leukocyte traffic. Glycosyltransferases involved in selectin ligand biosynthesis include the alpha1,3-fucosyltransferases FucT-VII and FucT-IV, one or more sialyltransferases, and at least one O-linked branching enzyme. Previous studies have shown that core 2 beta1-6-N-glucosaminyltransferase (C2GlcNAcT-I; EC 2.4.1.102) is required for functional modification of PSGL-1, the leukocyte P-selectin ligand, but have been ambiguous on whether this enzyme is involved in E-selectin ligand formation. Using an attachment and rolling assay under defined shear flow in vitro, this study shows that C2GlcNAcT-I(-) lymphoid cells stably transfected with FucT-VII complementary DNA attach and roll well on E-selectin at 1.5 dynes/cm.(2) Further, attachment and rolling on P-selectin of neutrophils is sharply reduced and that of short- term polarized Th1 cells is virtually abolished, with leukocytes from C2GlcNAcT-I(-/-) mice. In contrast, both neutrophils and Th1 cells from C2GlcNAcT-I(-/-) mice attach and roll as well as wild-type cells on E-selectin. These results show that C2GlcNAcT-I is selectively required for biosynthesis of ligands for P-selectin, but is not essential for at least some E-selectin ligands. Distinct requirements for C2GlcNAcT-I in the formation of ligands for E-selectin versus P-selectin represents a novel level of regulation of expression of selectin ligands and lymphocyte traffic. (Blood. 2001;97:3806-3811)
Assuntos
Selectina E/metabolismo , N-Acetilglucosaminiltransferases/biossíntese , N-Acetilglucosaminiltransferases/farmacologia , Selectina-P/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Fucosiltransferases/metabolismo , Fucosiltransferases/farmacologia , Humanos , Ligantes , Ativação Linfocitária/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , N-Acetilglucosaminiltransferases/metabolismo , Neutrófilos/citologia , Neutrófilos/fisiologia , Ligação Proteica/efeitos dos fármacos , Células Th1/citologia , Células Th1/fisiologia , TransfecçãoRESUMO
Hospitals would logically become leaders if the nation is to accept former Surgeon General C. Everett Koop's challenge to make its public institutions smoke-free by the year 2000. We tested whether printed materials, workshops, newsletters, and consultations could increase both the number of smoke-free hospitals in a state and the rate at which they became smoke-free. All acute-care hospitals in Minnesota (n = 166) were compared to a sample of 51 acute-care hospitals in a reference area, western Wisconsin, before and after a one-year campaign. While 2.4% of the hospitals in Minnesota were smoke-free before the campaign, none of the hospitals in the reference area sample was smoke-free at this time. Both areas experienced a significant increase in the proportion of hospitals that became smoke-free during the year--30.7% of the Minnesota hospitals and 15.7% of the hospitals in the reference area sample (p less than .01) were smoke-free after the one-year campaign--and the campaign did appear to marginally increase the rate of adoption in Minnesota over that of the reference area (p = .08). The results of this study indicate that smoke-free hospitals are feasible and that a statewide initiative can facilitate the hospitals' decision to become smoke-free.