title: Lack of tyrosylprotein sulfotransferase activity in hematopoietic cells drastically attenuates atherosclerosis in Ldlr-/- mice.
abstract: OBJECTIVE
  Leukocyte recruitment is a major contributor in the development of atherosclerosis and requires a variety of proteins such as adhesion molecules, chemokines, and chemokine receptors. Several key molecular players implicated in this process are expressed on monocytes and require protein-tyrosine sulfation for optimal function in vitro, including human CCR2, CCR5, CX3CR1, and PSGL-1. We therefore hypothesized that protein-tyrosine sulfation in hematopoietic cells plays an important role in the development of atherosclerosis.
  
  
  RESULTS
  Lethally-irradiated Ldlr(-/-) mice were rescued with hematopoietic progenitors lacking tyrosylprotein sulfotransferase (TPST) activity attributable to deletion of the Tpst1 and Tpst2 genes. TPST deficient progenitors efficiently reconstituted hematopoiesis in Ldlr(-/-) recipients and transplantation had no effect on plasma lipids on a standard or atherogenic diet. However, we observed a substantial reduction in the size of atherosclerotic lesions and the number of macrophages in lesions from hyperlipidemic Ldlr(-/-) recipients transplanted with TPST deficient progenitors compared to wild-type progenitors. We also document for the first time that murine Psgl-1 and Cx3cr1 are tyrosine-sulfated.
  
  
  CONCLUSIONS
  These data demonstrate that protein-tyrosine sulfation is an important contributor to monocytes/macrophage recruitment and/or retention in a mouse model of atherosclerosis.
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Andrew-Westmuckett@omrf.org
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Westmuckett
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Moore
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006949:Hyperlipidemias / Q000201:enzymology*; D007958:Leukocyte Count; D051379:Mice; D018345:Mice, Knockout; D011336:Probability; D011897:Random Allocation; D019707:Receptors, Chemokine / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism*
chemical_list: D019707:Receptors, Chemokine; D011973:Receptors, LDL; D015238:Sulfotransferases; C039079:protein-tyrosine sulfotransferase
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