title: Exposure to p,p'-DDE Alters Macrophage Reactivity and Increases Macrophage Numbers in Adipose Stromal Vascular Fraction.
abstract: Exposure to p,p'-DDE (DDE), the main bioaccumulative metabolite of the organochlorine insecticide p,p'-DDT, is associated with a higher prevalence of obesity, dyslipidemia, insulin resistance, metabolic syndrome, and immunomodulation. The present study was carried out to determine whether DDE perturbs adipose tissue homeostasis through modulation of macrophage function. Treatment with DDE or a cyclooxygenase-2 inhibitor prior to lipopolysaccharide exposure significantly decreased production of prostaglandins (PG) from J774a.1 macrophages in vitro. Similarly, J774A.1 cell lysates incubated with DDE or a specific cyclooxygenase-2 inhibitor (NS-398) produced significantly less PGE2 and PGF2α. Macrophage polarization studies revealed a pattern of DDE effects that were not fully consistent with a purely pro- or purely anti- M1 or M2 effect. However, DDE suppressed expression of two M1 markers (induced by an M1 stimulus) and enhanced expression of an M2 marker (induced by an M2 stimulus). Further studies including assessment of macrophage function are needed to fully characterize the effects of DDE on macrophage polarization. Obesity is characterized by an increase in the number of resident adipose tissue macrophages. To assess monocyte/macrophage recruitment to the adipose tissue in vivo, male C57Bl/6H mice were treated with 2 mg/kg DDE or corn oil vehicle for 5 days by gavage. Epididymal fat pads were digested and macrophage populations were analyzed by flow cytometry. In DDE-treated animals, there was a significant increase (37%) in F4/80(+)CD11b(+) macrophages/g of epididymal adipose over vehicle (P < .05). Together, these results suggest a role for DDE in the enhancement of adipose tissue macrophage recruitment and/or proliferation, as well as modulation of immune cell function that may contribute to the etiology of metabolic diseases associated with organochlorine exposure.
authors.affiliation: *Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine and.
authors.forename: Lauren H
authors.initials: LH
authors.lastname: Mangum
authors.affiliation: *Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine and.
authors.forename: John Allen
authors.initials: JA
authors.lastname: Crow
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi 39762-6100.
authors.forename: John V
authors.initials: JV
authors.lastname: Stokes
authors.affiliation: *Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine and.
authors.forename: George E
authors.initials: GE
authors.lastname: Howell
authors.affiliation: *Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine and.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Ross
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi 39762-6100.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Pruett
authors.affiliation: *Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine and chambers@cvm.msstate.edu.
authors.forename: Janice E
authors.initials: JE
authors.lastname: Chambers
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology; D001119:Arginase / Q000235:genetics; D039481:CD11b Antigen / Q000276:immunology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D015232:Dinoprostone / Q000096:biosynthesis*; D004785:Environmental Pollutants / Q000633:toxicity*; D004822:Epididymis / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D054467:Phospholipases A2 / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D039481:CD11b Antigen; D004785:Environmental Pollutants; D008070:Lipopolysaccharides; C036763:monocyte-macrophage differentiation antigen; D003633:Dichlorodiphenyl Dichloroethylene; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D054467:Phospholipases A2; C544448:Arg1 protein, mouse; D001119:Arginase; D015232:Dinoprostone
keywords: adipose; immunomodulation; macrophage; organochlorine; p,p′-DDE; prostaglandin