It has been shown that osteopontin (OPN) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). However, the molecular mechanism of OPN action is yet to be elucidated. Splenic monocytes obtained from arthritic mice exhibited a significant capacity for cell migration toward thrombin-cleaved OPN but not toward full-length OPN. Migratory monocytes expressed α9 and α4 integrins. Since cleavage of OPN by thrombin exposes the cryptic epitope recognized by α9 and α4 integrins, we investigated the role of the cryptic epitope SLAYGLR in a murine RA model by using a specific antibody (M5) reacting to SLAYGLR sequence. The M5 antibody could abrogate monocyte migration toward the thrombin-cleaved form of OPN. Importantly, M5 antibody could inhibit the proliferation of synovium, bone erosion, and inflammatory cell infiltration in arthritic joints. Thus, we demonstrated that a cryptic epitope, the SLAYGLR sequence of murine OPN, is critically involved in the pathogenesis of a murine model of RA

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~~ ~Aldehyde oxidase (AO; EC 1.2.3.1) that could oxidize indole-3-acetaldehyde into indole-3-acetic acid was purified approximately 2000-fold from coleoptiles of 3-d-old maize (Zea mays 1.) seedlings. The apparent molecular mass of the native enzyme was about 300 kD as estimated by gel-filtration column chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the enzyme was composed of 150-kD subunits. It contained flavin adenine dinucleotide, iron, and molybdenum as prosthetic groups and had absorption peaks in the visible region (300-600 nm). To our knowledge, this is the first demonstration of the presence of flavin adenine dinucleotide and metals i n plant AO. Other aromatic aldehydes such as indole-3-aldehyde and benzaldehyde also served as good substrates, but N-methylnicotinamide, a good substrate for animal AO, was not oxidized. 2-Mercaptoethanol, p-chloromercuribenzoate, and iodoacetate partially inhibited the activity, but well-known inhibitors of animal AO, such as menadione and estradiol, caused no reduction in activity. These results indicate that, although maize AO is similar to animal enzymes in molecular mass and cofactor components, it differs i n substrate specificity and susceptibility t o inhibitors. lmmunoblotting analysis with mouse polyclonal antibodies raised against the purified maize AO showed that the enzyme was relatively rich i n the apical region of maize coleoptiles. The possible role of this enzyme is discussed in relation to phytohormone biosynthesis in plants.AO (EC 1.2.3.1) has been extensively investigated in animals and microorganisms. The enzyme catalyzes the oxidation of a variety of aldehydes and N,-containing heterocycles in the presence of.0, or certain redox dyes (Rajagopalan and Handler, 1966; Hall and Krenitsky, 1986). The enzyme has also been reported to reduce diphenyl sulfoxides (Yoshihara and Tatsumi, 1986), aromatic heterocyclic compounds (Bauer and Howard, 1991), and oximes (Tatsumi and Ishigai, 1987). AO is similar t o xanthine dehydrogenase (oxidase) in being a multicomponent enzyme that contains a molybdenum cofactor, nonheme iron, and FAD as prosthetic groups. The enzyme is found in the small intestine and liver of animals and has been implicated in the detoxification of various xenobiotics, including certain cancer chemotherapeutic agents (Bauer and Howard, 1991;Stoddart and Levine, 1992; Hirao et al., 1994). The enzyme may also play a role in retinoic acid synthesis (Tomita et al., 1993; Huang and Ichikawa, 1994) and in the degradation of aromatic aldehydes formed as a result of lignin breakdown by a soil bacterium (Crawford et al., 1982) and snails (Large and Connock, 1994).However, in plants only a limited amount of information has been published concerning this enzyme, including studies of Auena coleoptiles (Rajagopal, 1971), potato tubers (Rothe, 1974), cucumber seedlings (Bower et al., 1978), and pea seedlings (Miyata et al., 1981). Much attention has been focused on this enzyme because of its possible involvement ...

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Infection by influenza A virus enhances sensitization to inhaled antigens and airway responsiveness in mice by means of mechanisms including CD8(+) cells and antigen-specific IgE.