title: Perivascular Macrophages Limit Permeability.
abstract: Perivascular cells, including pericytes, macrophages, smooth muscle cells, and other specialized cell types, like podocytes, participate in various aspects of vascular function. However, aside from the well-established roles of smooth muscle cells and pericytes, the contributions of other vascular-associated cells are poorly understood. Our goal was to ascertain the function of perivascular macrophages in adult tissues under nonpathological conditions.
  
  
  
  We combined confocal microscopy, in vivo cell depletion, and in vitro assays to investigate the contribution of perivascular macrophages to vascular function. We found that resident perivascular macrophages are associated with capillaries at a frequency similar to that of pericytes. Macrophage depletion using either clodronate liposomes or antibodies unexpectedly resulted in hyperpermeability. This effect could be rescued when M2-like macrophages, but not M1-like macrophages or dendritic cells, were reconstituted in vivo, suggesting subtype-specific roles for macrophages in the regulation of vascular permeability. Furthermore, we found that permeability-promoting agents elicit motility and eventual dissociation of macrophages from the vasculature. Finally, in vitro assays showed that M2-like macrophages attenuate the phosphorylation of VE-cadherin upon exposure to permeability-promoting agents.
  
  
  
  This study points to a direct contribution of macrophages to vessel barrier integrity and provides evidence that heterotypic cell interactions with the endothelium, in addition to those of pericytes, control vascular permeability.
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Huanhuan
authors.initials: H
authors.lastname: He
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Mack
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Esra
authors.initials: E
authors.lastname: Güç
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Warren
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Mario Leonardo
authors.initials: ML
authors.lastname: Squadrito
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Witold W
authors.initials: WW
authors.lastname: Kilarski
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Caroline
authors.initials: C
authors.lastname: Baer
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Freshman
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Austin I
authors.initials: AI
authors.lastname: McDonald
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Safiyyah
authors.initials: S
authors.lastname: Ziyad
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Melody A
authors.initials: MA
authors.lastname: Swartz
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.).
authors.forename: Michele
authors.initials: M
authors.lastname: De Palma
authors.affiliation: From the Department of Human Genetics (H.H.), Department of Molecular, Cell and Developmental Biology (J.J.M., C.M.W., R.D.F., A.I.M., S.Z., M.L.I.-A.), Molecular Biology Institute (M.L.I.-A.), and Jonsson Comprehensive Cancer Center (M.L.I.-A.), University of California, Los Angeles; Institute for Bioengineering (IBI) (E.G., M.A.S.) and The Swiss Institute for Experimental Cancer Research (ISREC) (M.L.S., C.B., M.A.S., M.D.P., M.L.I.-A.), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Switzerland; and Institute for Molecular Engineering and Ben May Department of Cancer Research, University of Chicago, IL (W.W.K., M.A.S.). arispe@mcdb.ucla.edu.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Iruela-Arispe
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism*; D002199:Capillary Permeability; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D003911:Dextrans / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008643:Mesentery / Q000098:blood supply*; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism; D010537:Peritoneum / Q000098:blood supply*; D010641:Phenotype; D010766:Phosphorylation; D012235:Rhodamines / Q000378:metabolism; D012867:Skin / Q000098:blood supply*; D013997:Time Factors; D014162:Transfection; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D010047:Ovalbumin; D012235:Rhodamines; D000099152:Cadherin 5; C009434:tetramethylrhodamine isothiocyanate
keywords: capillaries; capillary permeability; cell communication; endothelial cells; macrophages