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Published on: May 4, 2017
Elevated soluble ADAM8 in bronchoalveolar lavage fluid in patients with eosinophilic pneumonia
Osamu Matsuno1, Eishi Miyazaki, Shinichi Nureki
1Division of Respiratory Disease, Department of Brain and Nerve Science, Oita University Faculty of Medicine, Yufu City, Oita, Japan. matsuno@med.oita-u.ac.jp
Background:
ADAM (a disintegrin and metalloprotease) family members, characterized by a metalloprotease and a disintegrin domain, are membrane-anchored glycoproteins involved in proteolysis and cell adhesion. ADAM8 might have an important role in allergic inflammation. It can cleave a variety of substrates and is a sheddase for VCAM-1 and CD23, the low-affinity IgE receptors.
Methods:
To evaluate the contribution of ADAM8 to the pathogenesis of eosinophilic pneumonia (EP), we measured the concentrations of soluble ADAM8 (sADAM8) and its substrates, soluble VCAM-1 (sVCAM-1) and soluble CD23 (sCD23), in bronchoalveolar lavage fluid from patients with smoking-induced acute eosinophilic pneumonia (AEP), chronic idiopathic eosinophilic pneumonia (CEP), and drug-induced eosinophilic pneumonia (drug-EP).
Results:
The sADAM8 and sVCAM-1 concentrations were increased in AEP and CEP. The sCD23 concentration was elevated in AEP. In AEP, but not CEP, the sADAM8 concentration significantly correlated with those of both sVCAM and sCD23.
Conclusion:
The pathogenesis of AEP, CEP, and drug-EP was distinct with regard to ADAM8. Our results are the first to associate ADAM8 with eosinophilic responses and lung inflammation in humans.
Insights
ADAM8 is linked to eosinophilic lung inflammation. Elevated ADAM8 levels correlate with specific eosinophilic pneumonia types, suggesting its role in human allergic responses.
Area of Science:
- Immunology
- Biochemistry
- Pulmonology
Background:
- ADAM (a disintegrin and metalloprotease) proteins are key in proteolysis and cell adhesion.
- ADAM8, a specific member, is implicated in allergic inflammation and acts as a sheddase for VCAM-1 and CD23.
- VCAM-1 and CD23 are crucial in immune cell trafficking and allergic responses.
Purpose of the Study:
- To investigate the role of ADAM8 in the pathogenesis of eosinophilic pneumonia (EP).
- To quantify soluble ADAM8 (sADAM8) and its substrates (sVCAM-1, sCD23) in different EP subtypes.
- To establish correlations between sADAM8, sVCAM-1, and sCD23 levels in EP.
Main Methods:
- Measurement of sADAM8, sVCAM-1, and sCD23 in bronchoalveolar lavage fluid.
- Analysis of patient samples from acute eosinophilic pneumonia (AEP), chronic idiopathic eosinophilic pneumonia (CEP), and drug-induced eosinophilic pneumonia (drug-EP).
- Statistical correlation analysis between measured biomarker concentrations.
Main Results:
- Increased concentrations of sADAM8 and sVCAM-1 were observed in both AEP and CEP.
- Elevated sCD23 levels were specifically found in AEP.
- A significant positive correlation between sADAM8 and both sVCAM-1 and sCD23 was identified in AEP, but not in CEP.
Conclusions:
- The distinct patterns of ADAM8 involvement highlight differing pathogenetic mechanisms across EP subtypes.
- These findings represent the first evidence linking ADAM8 to human eosinophilic responses and lung inflammation.
- ADAM8 emerges as a potential biomarker and therapeutic target in specific forms of eosinophilic lung disease.
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