Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers

Vernooy, Juanita H. J.; Drummen, Nadja E.A.; Suylen, Robert Jan van; Cloots, Roy H. E.; Möller, Gertrude M.; Bracke, Ken R.; Zuyderduyn, Suzanne; Dentener, Mieke A.; Hiemstra, Pieter S.; Wouters, Emiel F.M.

doi:10.1136/thx.2007.085423

Cited by 97 publications

(86 citation statements)

References 43 publications

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“…Using immunohistochemistry, we show for the first time leptin localization in lung tissue of mice, revealing leptin expression in BECs, pneumocytes, alveolar macrophages, and bronchial and vascular smooth muscle cells. The findings of the current study are corroborated by our clinical data that showed that BECs, pneumocytes, and macrophages are a rich source of leptin in human peripheral lung (6). Moreover, the current murine study and our previous human study examining lung tissue and (primary) cell cultures together convincingly demonstrate that smoke is a trigger FIGURE 7.…”

Section: Discussionsupporting

confidence: 78%

“…Leptin was originally described as an adipocyte-derived hormone involved in regulating the balance between food intake and energy expenditure by activating its functional receptor (Ob-Rb) (7) in the hypothalamus (8). Recent studies reported that leptin secretion not only by adipocytes but also by various epithelial cell types, including bronchial epithelial cells (BECs) (6,9) and type II pneumocytes (6). The structure of leptin and its receptor classify leptin as a type I cytokine.…”

mentioning

confidence: 99%

“…Recent observations that leptin is actually present in induced sputum (25), proximal airway biopsies (9), and peripheral lung tissue (6) of COPD patients designate the lung as a peripheral site of action for leptin. In addition, we showed that exposure of cultured (primary) epithelial cells to CS concentrate, cytokines, or glucocorticoids resulted in increased expression of both leptin and Ob-Rb (6). In light of the immunomodulating role of leptin, leptin may regulate pulmonary immune function in chronic inflammatory airway diseases, such as COPD.…”

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confidence: 99%

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Leptin Modulates Innate and Adaptive Immune Cell Recruitment after Cigarette Smoke Exposure in Mice

Vernooy¹,

Bracke

Drummen³

et al. 2010

The Journal of Immunology

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Leptin, a pleiotropic type I cytokine, was recently demonstrated to be expressed by resident lung cells in chronic obstructive pulmonary disease patients and asymptomatic smokers. To elucidate the functional role of leptin in the onset of chronic obstructive pulmonary disease, we tested leptin-deficient ob/ob mice (C57BL/6), leptin receptor-deficient db/db mice (C57BKS), and littermates in a model of cigarette smoke (CS)-induced pulmonary inflammation. Wild-type (WT) C57BL/6 mice were exposed for 4 or 24 wk to control air or CS. Pulmonary leptin expression was analyzed by immunohistochemistry and real-time PCR. Pulmonary inflammation upon 4 wk CS exposure was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue of WT, ob/ob, and db/db mice. Immunohistochemical analysis revealed leptin expression in bronchial epithelial cells, pneumocytes, alveolar macrophages, and bronchial/vascular smooth muscle cells. The 4 and 24 wk CS exposure increased leptin expression in bronchial epithelial cells and pneumocytes versus air-exposed WT mice (p < 0.05). The 4 wk CS exposure resulted in increased accumulation of neutrophils, dendritic cells, macrophages, and lymphocytes in BALF and lung tissue of WT, ob/ob, and db/db mice. CS-exposed ob/ob and db/db mice showed in general higher numbers of neutrophils and lower numbers of CD4+, CD8+, and dendritic cells versus CS-exposed WT mice. Consistently, CXCL1 levels were enhanced in BALF of CS-exposed ob/ob and db/db mice versus WT mice (p < 0.05). Exogenous leptin administration completely restored the skewed inflammatory profile in ob/ob mice. These data reveal an important role of leptin in modulating innate and adaptive immunity after CS inhalation in mice.

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Section: Discussionsupporting

confidence: 78%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Leptin Modulates Innate and Adaptive Immune Cell Recruitment after Cigarette Smoke Exposure in Mice

Vernooy¹,

Bracke

Drummen³

et al. 2010

The Journal of Immunology

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“…Smoking is associated with inflammation and previous studies have shown elevated levels of systemic inflammatory markers, such as WBC count, CRP and fibrinogen, in active smokers (32). This is also true for leptin, which was found to increase in asymptomatic smokers (33). All these data raise the possibility that the high smoking prevalence among controls, might have masked the ongoing systemic inflammation in bronchiectasis patients of our cohort.…”

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confidence: 47%

Does airway colonization cause systemic inflammation in bronchiectasis?

Çöplü²

2011

Tuberk Toraks

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“…We found evidence of leptin and leptin receptor expression within airway epithelium. Previous reports have also shown that leptin and leptin receptor are expressed in airway epithelium (24), and bronchial expression of leptin is increased in chronic obstructive pulmonary disease (25,26). Leptin seems to be involved in embryonic lung growth and maturation (27,28), and in fibroproliferative responses in the lung to bleomycin (29).…”

Section: Discussionmentioning

confidence: 99%

Obesity and Asthma

Sideleva¹,

Suratt²,

Black³

et al. 2012

Am J Respir Crit Care Med

291

159

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Rationale: Obesity is a major risk factor for asthma; the reasons for this are poorly understood, although it is thought that inflammatory changes in adipose tissue in obesity could contribute to airway inflammation and airway reactivity in individuals who are obese. Objectives: To determine if inflammation in adipose tissue in obesity is related to late-onset asthma, and associated with increased markers of airway inflammation and reactivity. Methods: We recruited a cohort of obese women with asthma and obese control women. We followed subjects with asthma for 12 months after bariatric surgery. We compared markers in adipose tissue and the airway from subjects with asthma and control subjects, and changes in subjects with asthma over time. Measurements and Main Results: Subjects with asthma had increased macrophage infiltration of visceral adipose tissue (P , 0.01), with increased expression of leptin (P , 0.01) and decreased adiponectin (p , 0.001) when controlled for body mass index. Similar trends were observed in subcutaneous adipose tissue. Airway epithelial cells expressed receptors for leptin and adiponectin, and airway reactivity was significantly related to visceral fat leptin expression (rho ¼ 20.8; P , 0.01). Bronchoalveolar lavage cytokines and cytokine production from alveolar macrophages were similar in subjects with asthma and control subjects at baseline, and tended to increase 12 months after surgery. Conclusions: Obesity is associated with increased markers of inflammation in serum and adipose tissue, and yet decreased airway inflammation in obese people with asthma; these patterns reverse with bariatric surgery. Leptin and other adipokines may be important mediators of airway disease in obesity through direct effects on the airway rather than by enhancing airway inflammation.

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Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers

Abstract: ABSTRACT

Cited by 97 publications

References 43 publications

Leptin Modulates Innate and Adaptive Immune Cell Recruitment after Cigarette Smoke Exposure in Mice

Leptin Modulates Innate and Adaptive Immune Cell Recruitment after Cigarette Smoke Exposure in Mice

Does airway colonization cause systemic inflammation in bronchiectasis?

Obesity and Asthma

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