RESUMO
In contrast to adult mice immunized with influenza A virus strain WSN and plasmid expressing WSN hemagglutinin (HA) gene which developed primary and secondary anti-HA antibody responses, mice immunized as neonates with virus failed to produce anti-HA antibodies while those immunized with plasmid developed weak primary but strong secondary responses. Analysis of the frequency of HA-specific B clonotypes as well as their reactivity pattern (RP) showed that viral or genetic immunization of adults increased the frequency of clonotypes which exhibit broad RP. The most striking observation of our study is that immunization of neonates with plasmid leads to increased synthesis of anti-HA antibodies as well as to an increased frequency of clonotypes exhibiting an adult-like RP. In contrast, neonatal immunization with virus caused a long-lasting unresponsiveness and the few clonotypes stimulated in vitro exhibited only a monoreactive pattern. Isotype patterns of mAb are also diversified in the case of mice immunized with plasmid as neonates. Rapid replacement of neonatal with adult clonotypes may explain the significant survival of the mice immunized with plasmid and challenged 1 or 3 months later with lethal doses of virus.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Imunização/métodos , Animais , Animais Recém-Nascidos , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/sangue , Linfócitos B/imunologia , Células Clonais/imunologia , DNA Viral/administração & dosagem , DNA Viral/genética , Memória Imunológica , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genéticaRESUMO
Nitric oxide (NO) is a small messenger molecule synthesized by a family of enzymes, the nitric oxide synthases. Cyclooxygenases are a group of proinflammatory enzymes that release prostaglandins including prostaglandin E2 (PGE2). Both nitric oxide synthase and cyclooxygenase are involved in the inflammatory cascade of arthritis. However, the relationship between these two enzymes and their products has not been explored in articular cartilage. Here we show that in cultured bovine chondrocytes and explants of human osteoarthritic cartilage both nitric oxide synthase and cyclooxygenase activities were induced by the inflammatory mediators, lipopolysaccharide, and interleukin-1 beta or tumor necrosis factor-alpha. When nitric oxide synthase activity was inhibited, PGE2, synthesis was inhibited. NO donors also induced PGE2 synthesis and NO scavengers inhibited cyclooxygenase activity. Taken together, these results support the concept that PGE2 synthesis is directly related to NO formation and that NO may modulate cyclooxygenase activity in articular cartilage.
