Melanogenesis and associated cytotoxic reactions: Applications to insect innate immunity
Section snippets
Insect innate immunity
Vertebrate species possess both innate and adaptive immune mechanisms to detect and eliminate aberrant cells and pathogens, whereas invertebrates rely solely on innate immunity to combat infections (Janeway and Medzhitov, 2002; Ratcliffe and Whitten, 2004). Comparative cellular, molecular, and biochemical investigations have shown innate immunity to be a conserved mechanism of defense, involving common cell-signaling pathways, transcriptional elements, and cytotoxic effector responses (Beutler,
Melanogenesis
Melanin is derived from the oxidation of monophenols and diphenols and the ensuing polymerization of their respective orthoquinones, a cascade of reactions initiated by, or at least involving the participation of, certain host blood cells or hemocytes (Sugumaran, 2002). Little is known of the molecular mechanisms that activate hemocytes and initiate melanogenesis in response to infections. Typically, parasite-induced melanogenic responses are cell-mediated, very site-specific, and do not
Melanogenesis in insects
TYRs are widespread throughout the plant and animal kingdoms, and are often referred to in different groups as polyphenoloxidases, POs, phenolases, diphenol oxidases, or catechol oxidases. Unfortunately, these designations do not distinguish TYR from laccases, which catalyze the oxidation of both o-diphenols and p-diphenols, and also are frequently referred to as a polyphenoloxidases, or from catechol oxidases, which are binuclear type 3 copper proteins that only oxidize o-diphenols. In
Cytotoxic and cytoprotective properties of melanin
ROI and RNI generated during melanogenesis have been implicated, along with pigment precursors, in the killing of parasites by insects (Fritsche et al., 2001; Kumar et al., 2003; Lanz-Mendoza et al., 2002; Nappi and Ottaviani, 2000; Nappi and Sugumaran, 1993; Nappi and Vass, 1993; Nappi et al., 1995, Nappi et al., 2000; Whitten et al., 2001). As redox-active polymers, melanins engage in electron transfer processes with a variety of reducing or oxidizing species (O’Brien, 1991). Depending on the
Interactions of melanin intermediates with ROI and RNI
Autoxidations in biological systems frequently progress via univalent reductions, as a result of which O2− is produced by the leakage of electrons to molecular oxygen. This radical, which can spawn more reactive oxygen species, normally is produced in electron transport chains, in activated phagocytic cells via plasma membrane NADPH oxidase, and in the course of the activity of certain other enzymes, including xanthine oxidase, aldehyde oxidase, and cytochrome P450 (Fig. 4). Parasite-induced
Melanogenesis, cytotoxicity, and host and parasite strategies
The NADPH oxidase-mediated production of O2− and ensuing reactions of SOD to produce H2O2 represent critical early events in establishing immune competence. Accordingly, the virulence of a parasite may reside in its ability to directly or indirectly interfere with the production of O2− and H2O2. In many prokaryotic and eukaryotic organisms, antioxidant protection is provided by antioxidant enzymes (e.g., SOD; catalase, CAT; glutathione peroxidase, GP) and thiol reducing systems that shuttle
Metalloenzymes and site-specificity of cytoxic responses
The transport, activation, and metabolism of oxygen are critical processes that are mediated primarily by metalloproteins containing iron or copper (Chevion et al., 1999). Investigations of the interactions of SQ− with metalloenzymes may define a mechanism for target-specific killing during melanogenesis. Enzyme-specific binding to substrate-like molecules expressed on foreign surfaces would localize any cytotoxic molecules generated by the active enzyme. In this context, tyrosine residues in
Concluding remarks
The molecular and biochemical changes that appear to be crucial to the host in establishing resistance, or to the parasite for its virulence, are merely temporal features of an ongoing struggle involving the interacting genomes of co-evolving combatants. Innate immunity is the sole mechanism of defense used by invertebrates to destroy infectious agents and rogue cells. Invertebrate blood cells or hemocytes exhibit macrophage-like activity and use ROI and RNI to destroy pathogens. These
Acknowledgements
The work of AJN was supported by the National Science Foundation (IBN 0342304) and the National Institutes of Health (GM 059774), and of BMC by the National Institutes of Health (AI 19769, AI 46032, and AI 53772). We thank M. Mastore and L. Kohler for their assistance with the manuscript, and the anonymous referees for their helpful comments and suggestions.
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