Respiratory protein-generated reactive oxygen species as an antimicrobial strategy

Nature Immunology 8, 1114 – 1122, 2007

Speaker: 謝政原                                                                           Time: 13:00~14:00, Nov. 7, 2007

Commentator: 胥直利 老師                           Place: Room 601

Abstract:

  To effectively invade host and escape from host immune defense, microbial pathogens have evolved several strategies, such as secretion of virulence factors. On the other hand, host immune system has also developed many counterplots, including the production of toxic reactive oxygen species (ROS). ROS-mediated microbial killing is an effective defense mechanism. Recent studies have shown that hemocyanin (HMC) and hemoglobin (Hb) in the invertebrates and vertebrates, respectively, can produce ROS. The HMC of horseshoe crab, an ancient protostome, possessed prophenoloxidase (PPO) potential that can be activated to phenoloxidase (PO) by microbes and lead to the generation of cytotoxic quinone, an equivalent of ROS produced in vertebrates. Hb has a pseudoperoxidase activity and produces superoxide ion when it is auto-oxidized to methemoglobin (metHb). However, the regulation of ROS production through microbial virulence factors and the role of ROS-mediated microbial killing in immune system are not fully clear. In this study, the authors found that the PPO activity of horseshoe crab’s HMC was induced by microbial proteases and further reinforced by pathogen-associated molecular patterns (PAMPs) that trigger the innate immune responses. Meanwhile, they observed different conformational changes of HMC after the addition of microbial proteases and PAMPs in various sequential orders. Microbial protease-inducing PPO effectively cleared the pathogen in vitro and in vivo. The pseudoperoxidase activity of mammalian metHb was similarly activated by microbial proteases and enhanced by PAMPs. In addition, hemolysis of mammalian red blood cells by the bacterial hemolysins is crucial for the ROS production and microbicidal function. Collectively, they demonstrated a mode of immune mechanism that directly responds to microbial proteases and eliminates the invaders. Since this mechanism has been found in the horseshoe crabs that have existed for over 500 million years, it maybe a primordial form of innate immunity conserved to nowadays.

References:

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2.            Kawano, T., Pinontoan, R., Hosoya, H. and Muto, S. Monoamine-dependent production of reactive oxygen species catalyzed by pseudoperoxidase activity of human hemoglobin. Biosci. Biotechnol. Biochem. 66, 1224–1232 (2002).