Abnormal pulmonary granuloma formation in osteopontin-deficient mice.
Osteopontin is a novel cytokine that is expressed in pulmonary granulomatous disease such as sarcoidosis and tuberculosis. It can regulate macrophage and T cell migration, activation, and cytokine expression, yet its role in granuloma formation and evolution is unknown. We induced hypersensitivity pulmonary granulomas by embolizing Schistosoma mansoni eggs to the lungs of osteopontin-deficient (null mutant) mice and osteopontin-sufficient (wild-type control) mice. Granulomas from osteopontin-null animals were smaller at early time points and contained remarkably few macrophages and macrophage-derived epithelioid cells and giant cells. T cell accumulation was unaffected by osteopontin deficiency. These results demonstrate that osteopontin regulates macrophage accumulation during pulmonary granuloma formation, and may explain the impaired ability of osteopontin-deficient hosts to control mycobacterial disease.
O'Regan
A W
AW
Pulmonary Center and Department of Pathology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Hayden
J M
JM
Body
S
S
Liaw
L
L
Mulligan
N
N
Goetschkes
M
M
Berman
J S
JS
D000818:Animals; D002452:Cell Count; D016207:Cytokines / Q000172:deficiency / Q000502:physiology*; D004847:Epithelial Cells / Q000473:pathology; D015726:Giant Cells / Q000473:pathology; D006099:Granuloma / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D007114:Immunization; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008171:Lung Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D053495:Osteopontin; D012550:Schistosoma mansoni / Q000276:immunology; D012795:Sialoglycoproteins / Q000172:deficiency / Q000502:physiology*; D013601:T-Lymphocytes / Q000473:pathology
D016207:Cytokines; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin