Increased serum ADAM8 concentration in patients with drug-induced eosinophilic pneumonia-ADAM8 expression depends on a the allergen route of entry.
BACKGROUND
ADAM8 (a disintegrin and a metalloprotease 8) has been linked to asthma and eosinophilic pneumonia (EP). ADAM8 cleaves a variety of substrates and is a sheddase for CD23, the low affinity IgE receptor. The concentration of soluble ADAM8 (sADAM8) is increased in bronchoalveolar lavage fluid (BALF) from patients with smoking-induced acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP), but not drug-induced EP (Drug-EP). In AEP, the BALF sADAM8 concentration significantly correlates with the soluble CD23 concentration (sCD23).


METHODS
To evaluate the involvement of ADAM8 in the pathogenesis of eosinophilic pneumonia, we measured the concentrations of sADAM8 and its substrate, soluble CD23 (sCD23), in serum from patients with AEP, CEP, and Drug-EP. We also measured the change in the sADAM8 concentration after a provocation test.


RESULTS
In contrast to the BALF findings, serum sADAM8 concentrations were increased in Drug-EP (mean+/-SEM; 639.6+/-49.15) and serum ADAM8 levels correlated positively with the serum sCD23 levels in patients with Drug-EP (P=0.0080, R(2)=0.8465). Serum sADAM8 concentrations were also increased in AEP (409+/-76.91) and CEP (644.7+/-87.03). Serum ADAM8 concentrations were also elevated after the provocation test.


CONCLUSIONS
Serum ADAM8 concentrations were elevated in Drug-EP, although the sADAM8 concentrations were not increased in the BALF in Drug-EP. Thus, the pathogenesis of AEP and Drug-EP may be distinct with regard to allergen exposure; AEP may be caused by the inhalation of antigens, whereas Drug-EP may be caused by bloodstream antigens. These findings indicate that ADAM8 levels reflect the route of eosinophilic inflammation in EP.
Matsuno
Osamu
O
Division of Respiratory Disease, Osaka Minami Medical Center, Kidohigashimachi 2-1, Kawachinagano city, Osaka 586-8521, Japan. matsuno@med.oita-u.ac.jp
Ono
Emiko
E
Ueno
Takuya
T
Takenaka
Ryuichi
R
Nishitake
Takahiro
T
Hiroshige
Shigeo
S
Miyazaki
Eishi
E
Kumamoto
Toshihide
T
Higuchi
Yasunori
Y
D051722:ADAM Proteins / Q000097:blood* / Q000276:immunology; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood* / Q000276:immunology; D008875:Middle Aged; D011657:Pulmonary Eosinophilia / Q000097:blood* / Q000139:chemically induced / Q000276:immunology; D017455:Receptors, IgE / Q000097:blood*; D012189:Retrospective Studies; D055815:Young Adult
D015415:Biomarkers; D008565:Membrane Proteins; D017455:Receptors, IgE; D051722:ADAM Proteins; C068490:ADAM8 protein, human