title: Diet-induced obesity alters myeloid cell populations in naïve and injured lung.
abstract: BACKGROUND
  There are pulmonary consequences to obesity, including increased prevalence of asthma, greater susceptibility to influenza, and possibly reduced susceptibility to lung injury. Although it is well established that obesity is associated with alterations to the immune system, little is known about obesity-associated changes to pulmonary immune cells.
  
  
  OBJECTIVE
  We hypothesized that obesity would alter the inflammatory milieu in the unchallenged lung and circulation; thereby contributing to altered susceptibility to lung injury.
  
  
  METHODS
  We used a murine model of diet-induced obesity and evaluated bone marrow and blood leukocytes at 3 months, and pulmonary leukocytes at 3 and 6 months for changes in their adhesion and chemokine receptors, markers of activation states, and cell numbers. We also evaluated the inflammatory response to LPS in obese mice.
  
  
  RESULTS
  In the lung, diet-induced obesity was associated with increased leukocyte numbers over-time. Adhesion receptors were increased in a cell- and site-specific fashion, and there was an evolution of macrophage and neutrophil polarization toward M1 and N1, respectively. After LPS-challenge, obesity was associated with increased neutrophil recruitment to the lung with impaired migration into the alveolar space. Associated with these changes, obesity increased LFA-1 and ICAM-1 neutrophil expression and altered CXCL1 gradients.
  
  
  CONCLUSIONS
  Our results highlight the effects of diet-induced obesity on the murine blood and lung leukocyte populations, including increases in adhesion receptor expression that may contribute to altered recruitment or retention within the lung. Translation of these findings to people with obesity will be critical for determining the basic inflammatory underpinnings of pulmonary disease susceptibility.
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, University of Washington, 850 Republican Avenue, Seattle, WA, 98115, USA. Manicone@uw.edu.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Manicone
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, University of Washington, 850 Republican Avenue, Seattle, WA, 98115, USA.
authors.forename: Keqin
authors.initials: K
authors.lastname: Gong
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, University of Washington, 850 Republican Avenue, Seattle, WA, 98115, USA.|Northwestern University, Chicago, IL, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Johnston
authors.affiliation: Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, University of Washington, 850 Republican Avenue, Seattle, WA, 98115, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Giannandrea
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D049109:Cell Proliferation; D004041:Dietary Fats; D005260:Female; D008168:Lung / Q000276:immunology* / Q000473:pathology; D055370:Lung Injury / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D009765:Obesity / Q000276:immunology* / Q000473:pathology
chemical_list: D004041:Dietary Fats