Am J Respir Crit Care Med. 2012 Jul 5. [Epub ahead of print]
Alveolar Macrophages from Overweight/Obese Asthmatic Subjects Demonstrate a Pro-inflammatory Phenotype.
Lugogo NL, Hollingsworth JW, Howell DL, Que LG, Francisco D, Church TD, Potts-Kant EN, Ingram JL, Wang Y, Jung SH, Kraft M.
Source
Medicine, Duke University, Durham, North Carolina, United States.
Abstract
RATIONALE:
Obesity is associated with increased prevalence and severity of asthma. Adipose tissue macrophages can contribute to the systemic pro-inflammatory state associated with obesity. However, it remains unknown whether alveolar macrophages have a unique phenotype in overweight/obese asthmatic patients.
OBJECTIVE:
We hypothesized that leptin levels would be increased in the bronchoalveolar lavage fluid from overweight/obese subjects and furthermore that leptin would alter the response of alveolar macrophages to bacterial lipopolysaccharide.
METHODS:
Forty-two asthmatic subjects and forty-six healthy controls underwent research bronchoscopy. Bronchoalveolar lavage fluid from sixty-six was analyzed for the level of cellular inflammation, cytokines, and soluble leptin. Cultured primary macrophages from twenty-two subjects were exposed to LPS, leptin, or leptin + LPS. Cytokines were measured in the supernatants.
RESULTS:
Leptin levels were increased in overweight/obese subjects regardless of asthma status (p=0.013), but were significantly higher in overweight/obese asthmatics. Observed levels of TNF-α were highest in overweight/obese asthmatic subjects. Ex vivo studies of primary alveolar macrophages identify that the response to LPS was most robust in alveolar macrophages from overweight/obese asthmatic subjects and pre-exposure to high-dose leptin enhanced the pro-inflammatory response. Leptin alone was sufficient to induce production of pro-inflammatory cytokines from macrophages derived from overweight/obese asthmatic subjects.
CONCLUSIONS:
Ex vivo studies support that alveolar macrophages derived from overweight/obese asthmatic subjects are uniquely sensitive to leptin. This macrophage phenotype in context of higher levels of soluble leptin may contribute to the pathogenesis of airways disease associated withobesity.
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