Abstract
BackgroundThere 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.ObjectivesWe hypothesized that obesity would alter the inflammatory milieu in the unchallenged lung and circulation; thereby contributing to altered susceptibility to lung injury.MethodsWe 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.ResultsIn 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.ConclusionOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0341-8) contains supplementary material, which is available to authorized users.
Highlights
There are pulmonary consequences to obesity, including increased prevalence of asthma, greater susceptibility to influenza, and possibly reduced susceptibility to lung injury
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
Diet-induced obesity is associated with an increase in monocytes and lymphocytes in the circulation at 3 months C57Bl/6J male mice were maintained on a Western diet comprised of 42 % fat (HFD) for 3 months
Summary
There are pulmonary consequences to obesity, including increased prevalence of asthma, greater susceptibility to influenza, and possibly reduced susceptibility to lung injury. There is increased macrophage recruitment to adipose tissue with progressive repolarization from M2 to M1 cells [10,11,12], increased systemic proinflammatory mediators, and a leukocytosis with elevated lymphocytes, neutrophils and monocytes reported in both obese children and adults [13]. We report on the differential leukocyte recruitment to the lung post-LPS challenge, with a dramatic increase in neutrophil sequestration to the lung in obese mice with impaired cell migration into the alveolar space. These studies highlight the profound alterations of the pulmonary immune cells associated with obesity, and future studies are needed to translate these findings to human pulmonary disease
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