L-selectin deficiency decreases aortic B1a and Breg subsets and promotes atherosclerosis

Breanne N. Gjurich; Parésa L. Taghavie-Moghadam; Klaus Ley; Elena V. Galkina

doi:10.1160/TH13-10-0865

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 112(04): 803-811
DOI: 10.1160/TH13-10-0865

Animal Models

Schattauer GmbH

L-selectin deficiency decreases aortic B1a and B_reg subsets and promotes atherosclerosis

Breanne N. Gjurich

¹Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, USA

,

Parésa L. Taghavie-Moghadam

¹Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, USA

,

Klaus Ley

²Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA

,

Elena V. Galkina

¹Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, USA

› Author Affiliations

Abstract

Summary

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.

Keywords

Atherosclerosis - L-selectin - B cell subsets

Full Text

References

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