title: β3-Adrenergic receptor stimulation induces E-selectin-mediated adipose tissue inflammation.
abstract: Inflammation induced by wound healing or infection activates local vascular endothelial cells to mediate leukocyte rolling, adhesion, and extravasation by up-regulation of leukocyte adhesion molecules such as E-selectin and P-selectin. Obesity-associated adipose tissue inflammation has been suggested to cause insulin resistance, but weight loss and lipolysis also promote adipose tissue immune responses. While leukocyte-endothelial interactions are required for obesity-induced inflammation of adipose tissue, it is not known whether lipolysis-induced inflammation requires activation of endothelial cells. Here, we show that β(3)-adrenergic receptor stimulation by CL 316,243 promotes adipose tissue neutrophil infiltration in wild type and P-selectin-null mice but not in E-selectin-null mice. Increased expression of adipose tissue cytokines IL-1β, CCL2, and TNF-α in response to CL 316,243 administration is also dependent upon E-selectin but not P-selectin. In contrast, fasting increases adipose-resident macrophages but not neutrophils, and does not activate adipose-resident endothelium. Thus, two models of lipolysis-induced inflammation induce distinct immune cell populations within adipose tissue and exhibit distinct dependences on endothelial activation. Importantly, our results indicate that β(3)-adrenergic stimulation acts through up-regulation of E-selectin in adipose tissue endothelial cells to induce neutrophil infiltration.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Roth Flach
authors.forename: Anouch
authors.initials: A
authors.lastname: Matevossian
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Akie
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Negrin
authors.forename: Marina T
authors.initials: MT
authors.lastname: Paul
authors.forename: Michael P
authors.initials: MP
authors.lastname: Czech
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007107:Immune System; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D008066:Lipolysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D019040:E-Selectin; D053583:Interleukin-1beta; D022702:Receptors, Adrenergic, beta-3; D014409:Tumor Necrosis Factor-alpha