Elevated soluble ADAM8 in bronchoalveolar lavage fluid in patients with eosinophilic pneumonia.
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.


CONCLUSIONS
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.
Matsuno
Osamu
O
Division of Respiratory Disease, Department of Brain and Nerve Science, Oita University Faculty of Medicine, Yufu City, Oita, Japan. matsuno@med.oita-u.ac.jp
Miyazaki
Eishi
E
Nureki
Shinichi
S
Ueno
Takuya
T
Ando
Masaru
M
Ito
Kazunobu
K
Kumamoto
Toshihide
T
Higuchi
Yasunori
Y
D051722:ADAM Proteins / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D017252:CD3 Complex; D008565:Membrane Proteins; D019010:Vascular Cell Adhesion Molecule-1; D051722:ADAM Proteins; C068490:ADAM8 protein, human