Distinct roles of osteopontin fragments in the development of the pulmonary involvement in sarcoidosis.
Osteopontin (OPN) is a secreted glycoprotein with cell adhesive and chemoattractive functions and is expressed in granulomas of sarcoidosis. It is well documented that full-length OPN (F-OPN) is susceptible to proteolytic fragmentation resulting in carboxyl-terminal OPN (C-OPN). We have previously revealed that C-OPN suppresses cell adhesion mediated by F-OPN. However, the implication of F-OPN and C-OPN in the progression of pulmonary involvement in sarcoidosis has not yet been elucidated. In this study, we demonstrated that (l) OPN was expressed in granulomas of sarcoidosis, (2) plasma F-OPN level in patients with sarcoidosis, especially in stage II patients, was significantly elevated compared with those of the controls, (3) plasma C-OPN levels in patients of stages 0, I, and III were significantly higher than those of the controls, and (4) in vitro recombinant F-OPN induces macrophage migration and that C-OPN inhibits cell migration mediated by F-OPN. These results suggest that F-OPN may promote granuloma formation in sarcoidosis, while C-OPN may suppress it. Thus, OPN and its fragment may play distinct roles in the development of sarcoidosis.
Maeda
K
K
Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Takahashi
K
K
Takahashi
F
F
Tamura
N
N
Maeda
M
M
Kon
S
S
Uede
T
T
Fukuchi
Y
Y
D016022:Case-Control Studies; D002448:Cell Adhesion; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053495:Osteopontin; D017565:Sarcoidosis, Pulmonary / Q000209:etiology*; D012795:Sialoglycoproteins / Q000097:blood / Q000737:chemistry / Q000502:physiology*
C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin