title: Endothelial Protective Monocyte Patrolling in Large Arteries Intensified by Western Diet and Atherosclerosis.
abstract: BACKGROUND
  Nonclassical mouse monocyte (CX3CR1high, Ly-6Clow) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Because of technical challenges, it is currently not established how patrolling occurs in large arteries.
  
  
  OBJECTIVE
  This study was undertaken to elucidate the molecular, migratory, and functional phenotypes of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic, and atherosclerotic conditions.
  
  
  RESULTS
  Applying a new method for stable, long-term 2-photon intravital microscopy of unrestrained large arteries in live CX3CR1-GFP (green fluorescent protein) mice, we show that nonclassical monocytes patrol inside healthy carotid arteries at a velocity of 36 μm/min, 3× faster than in microvessels. The tracks are less straight but lead preferentially downstream. The number of patrolling monocytes is increased 9-fold by feeding wild-type mice a Western diet or by applying topical TLR7/8 (Toll-like receptor) agonists. A similar increase is seen in CX3CR1+/GFP/apoE-/-mice on chow diet, with a further 2- to 3-fold increase on Western diet (22-fold over healthy). In plaque conditions, monocytes are readily captured onto the endothelium from free flow. Stable patrolling is unaffected in CX3CR1-deficient mice and involves the contribution of LFA-1 (lymphocyte-associated antigen 1) and α4integrins. The endothelial damage in atherosclerotic carotid arteries was assessed by electron microscopy and correlates with the number of intraluminal patrollers. Abolishing patrolling monocytes in Nr4a1-/-apoE-/-mice leads to pronounced endothelial apoptosis.
  
  
  CONCLUSIONS
  Arterial patrolling is a prominent new feature of nonclassical monocytes with unique molecular and kinetic properties. It is highly upregulated in hyperlipidemia and atherosclerosis in a CX3CR1-independent fashion and plays a potential role in endothelial protection.
authors.affiliation: From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.).
authors.forename: Amado
authors.initials: A
authors.lastname: Quintar
authors.affiliation: From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.).
authors.forename: Sara
authors.initials: S
authors.lastname: McArdle
authors.affiliation: From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.).
authors.forename: Dennis
authors.initials: D
authors.lastname: Wolf
authors.affiliation: From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.).
authors.forename: Alex
authors.initials: A
authors.lastname: Marki
authors.affiliation: From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.).
authors.forename: Erik
authors.initials: E
authors.lastname: Ehinger
authors.affiliation: From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.).
authors.forename: Melanie
authors.initials: M
authors.lastname: Vassallo
authors.affiliation: From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.).
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Miller
authors.affiliation: From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.).
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Mikulski
authors.affiliation: From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.).
authors.forename: Klaus
authors.initials: K
authors.lastname: Ley
authors.affiliation: From the La Jolla Institute for Allergy and Immunology, Division of Inflammation Biology, La Jolla, CA (A.Q., S.M., D.W., A.M., E.E., M.V., J.M., Z.M., K.L., K.B.); and Centro de Microscopia Electronica, INICSA-CONICET, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Cordoba, Argentina (A.Q.). konrad@lji.org klaus@lji.org.
authors.forename: Konrad
authors.initials: K
authors.lastname: Buscher
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D066273:Diet, Western / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000172:deficiency*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine
keywords: apoptosis; atherosclerosis; endothelium; homeostasis; inflammation