J Asthma. 2013 Oct;50(8):828-35.

Adiponectin attenuates human eosinophil adhesion and chemotaxis: implications in allergic inflammation.

Yamamoto R, Ueki S, Moritoki Y, Kobayashi Y, Oyamada H, Konno Y, Tamaki M, Itoga M, Takeda M, Ito W, Chihara J.

Department of Infection, Allergy, Clinical Immunology and Laboratory Medicine, Akita University Graduate School of Medicine , Akita , Japan.



OBJECTIVE: Growing evidence has shown an association between obesity and asthma. Adiponectin, an adipocyte-derived cytokine, is known to have anti-inflammatory effects with reduced concentrations in obese subjects. Recent findings raised the intriguing possibility that adiponectin might play a role in allergic inflammation, although the mechanistic basis for their relationship remains unclear. The purpose of this study was to examine whether adiponectin might affect functions of eosinophils, which play an important role in the pathogenesis of asthma.

METHODS: Human peripheral blood eosinophils were purified to study expression of adiponectin receptors AdipoR1 and AdipoR2 using RT-PCR and flow cytometry. The effect of adiponectin on eosinophil survival was investigated using annexin V and propidium iodide staining. Eotaxin-induced cell adhesion was investigated using ICAM-1-coated plates. A Boyden chamber and real-time horizontal migration system were used for eotaxin-directed chemotaxis assay. Expression of eotaxin receptor CCR3 and intracellular calcium influx were assessed by flow cytometry.

RESULTS: AdipoR1 and AdipoR2 were expressed in human eosinophils. Adiponectin did not affect eosinophil survival or CCR3 expression; however, eotaxin-enhanced adhesion was inhibited by pretreatment with adiponectin. Adiponectin also diminished eotaxin-directed chemotactic responses by disturbing both velocity and directionality. Calcium influx in response to eotaxin was attenuated by adiponectin.

CONCLUSIONS: These results indicate that adiponectin attenuates the eosinophil functions induced by eotaxin without affecting cell viability. The inhibitory effect was associated with diminished calcium signaling rather than altering of surface receptor expression. Increasing circulating adiponectin might be a novel therapeutic modality for treatment of asthma, especially in obese asthmatics.

PMID: 23777560



Obesity is associated with asthma, in terms of increased prevalence, reduction in lung functions, and reduced response to medication. Adiponectin is an adipocytokine mainly secreted by adipocytes; however, a decreased level of serum adiponectin is observed in obese subjects. This article is the first demonstration of the expression of adiponectin receptors and involvement of adiponectin in anti-inflammatory effect on human eosinophils. Our data also support the findings of previous reports showing the favorable role of adiponectin in allergic response.

Contrary to adiponectin, increased levels of the adipocytokine leptin are observed in obese humans. We have previously shown that leptin has pro-inflammatory effects on eosinophils (Kato et al., Int Arch Allergy Immunol 155: 335-344). Thus, these adipocytokines appear to play a role in adipocyte-eosinophil interaction.

Shigeharu Ueki-pic1



Figure 1. Increasing adiponectin attenuates eosinophilic functions.

Weight loss leads to increased adiponectin levels. Administration of peroxisome-proliferator activated receptor-g (PPARg) agonists such as thiazolidinediones, currently used as therapeutics in diabetes, is also known to increase circulating adiponectin levels. These approaches might be a therapeutic modality for treatment of allergic inflammation, especially in obese asthmatics.

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