title: L-selectin deficiency decreases aortic B1a and Breg subsets and promotes atherosclerosis.
abstract: There is a significant recruitment of leucocytes into aortas during atherogenesis. L-selectin regulates leucocyte migration into secondary lymphoid and peripheral tissues and was proposed to play a role in leucocyte homing into aortas. Here, we determine the role of L-selectin in atherosclerosis. L-selectin-deficient Apoe-/- (Sell-/-Apoe-/-) mice had a 74% increase in plaque burden compared to Apoe-/- mice fed a chow diet for 50 weeks. Elevated atherosclerosis was accompanied by increased aortic leucocyte content, but a 50% reduction in aortic B cells despite elevated B cell counts in the blood. Follicular B cells represented 65%, whereas B1a and regulatory B cells (Breg) comprised 5% of aortic B cells. B1a and Breg cell subsets were reduced in Sell-/-Apoe-/- aortas with accompanied two-fold decrease in aortic T15 antibody and 1.2-fold decrease of interleukin-10 (IL-10) levels. L-selectin was required for B1 cell homing to the atherosclerotic aorta, as demonstrated by a 1.5-fold decrease in the migration of Sell-/-Apoe-/- vs Apoe-/- cells. Notably, we found a 1.6-fold increase in CD68hi macrophages in Sell-/-Apoe-/- compared to Apoe-/- aortas, despite comparable blood monocyte numbers and L-selectin-dependent aortic homing. L-selectin had no effect on neutrophil migration into aorta, but led to elevated blood neutrophil numbers, suggesting a potential involvement of neutrophils in atherogenesis of Sell-/-Apoe-/- mice. Thus, L-selectin deficiency increases peripheral blood neutrophil and lymphocyte numbers, decreases aortic B1a and Breg populations, T15 antibody and IL-10 levels, and increases aortic macrophage content of Sell-/-Apoe-/- mice. Altogether, these data provide evidence for an overall atheroprotective role of L-selectin.
authors.forename: Breanne N
authors.initials: BN
authors.lastname: Gjurich
authors.forename: Parésa L
authors.initials: PL
authors.lastname: Taghavie-Moghadam
authors.forename: Klaus
authors.initials: K
authors.lastname: Ley
authors.affiliation: Elena V. Galkina, PhD, Associate Professor, Dept. Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, USA, Tel.: +1 757 446 5019, Fax: +1 757 624 2255, E-mail: galkinev@evms.edu.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Galkina
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology; D060151:B-Lymphocytes, Regulatory / Q000166:cytology*; D002465:Cell Movement; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D019041:L-Selectin / Q000097:blood* / Q000235:genetics*; D007962:Leukocytes / Q000166:cytology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology; D009504:Neutrophils / Q000166:cytology; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001057:Apolipoproteins E; D016753:Interleukin-10; D019041:L-Selectin; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Atherosclerosis; B cell subsets; L-selectin