title: Osteopontin is dispensable for protection against high load systemic fungal infection.
abstract: Osteopontin (OPN) is a multi-functional cytokine which is involved in the pathogenesis of autoimmune disease. We previously reported that thrombin-cleaved form of OPN plays a pathogenic role in murine model of rheumatoid arthritis (RA) by using neutralizing antibody (M5) reacting against the cryptic epitope within OPN, exposed by thrombin cleavage of OPN. It has been shown that OPN-deficient mice are susceptible to various infections, demonstrating the protective role of OPN against various infectious diseases. However, it remains to be clarified whether and how OPN is involved in protection against systemic fungal infection. In a murine model of systemic fungal infection, OPN-deficient mice showed the increase in the susceptibility to low load, but not to high load fungal infection, indicating the protective of OPN against mild or severe forms of infections. However, mice treatment with M5 antibody did not alter the susceptibility to both high and low load fungal infection. These experiments suggest that in sharp contrast to the complete abrogation of OPN expression in OPN-deficient mice, the neutralization of OPN by antibody against thrombin-cleaved form of OPN does not interfere with the host defense against high and low load fungal infection. These findings suggest that the neutralizing antibody which is specific for the epitope of thrombin-cleaved OPN may become an attractive therapeutic means for the treatment of RA without interfering host defense system.
authors.affiliation: Fermentation Research Laboratories, Astellas Pharmaceutical Inc., Tokodai 5-2-3, Tsukuba, Ibaraki, 300-2698, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Sato
authors.forename: Nobuchika
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rittling
authors.forename: David T
authors.initials: DT
authors.lastname: Denhardt
authors.forename: Motohiro
authors.initials: M
authors.lastname: Hino
authors.forename: Junko
authors.initials: J
authors.lastname: Morimoro
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sakai
authors.forename: Akihiko
authors.initials: A
authors.lastname: Fujie
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009181:Mycoses / Q000517:prevention & control*; D053495:Osteopontin / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D015398:Signal Transduction / Q000502:physiology; D013583:Synovial Membrane / Q000276:immunology
chemical_list: D000906:Antibodies; D053495:Osteopontin