Phenoloxidase system explained

Phenoloxidase system is a major defense system in many invertebrates which ultimately leads to melanization of pathogens and damaged tissues. The process of melanization depends on activation of the enzyme phenoloxidase (PO) which is controlled by the prophenoloxidase (proPO) activation system. ^[1]

During activation of the proPO cascade, many other immune reactions are produced, such as cytotoxic, opsonic and encapsulation activities.^[2] The phenoxidase cascade plays an important role in invertebrates (especially insects) in three physiologically important processes: immune reactions, sclerotization of the cuticle and wound healing.^[3]

Prophenolxidase activation system

The phenoloxidase system begins with the recognition of microbial PAMPs (pathogen-associated molecular patterns) including LPS (gram-negative bacteria), peptidoglycans (gram-positive bacteria) and β-1,3-glucans (fungi). Interaction of PAMPs with PRPs (pattern-recognition proteins) activates a series of serine proteinases and those proteolytically cleave the prophenoloxidase (proPO) zymogen and activate phenoxidase (PO).

During the proPO system activation, reactive intermediates such as quinone-like intermediates, reactive oxygen (ROI) or nitrogen intermediates are produced. These have cytotoxic activity against microorganisms, prevent organism from entering of another pathogen and also assist in wound healing.^{[4] [5]}

Melanization process

Active PO plays an important role in the initial stages of the melanization process. The PO catalyses a hydroxylation of monophenols (tyrosine) on diphenols and oxidation of diphenols to dichinones. The chinones non-enzymatically change their structure to dopachrome and than dopachrome isomerase changes dopachrome to indole. In the final phase of the process melanin is made by an oxidation and a polymerization.^{[6] [7]} Melanin is rapidly deposited around the pathogen, thereby limiting its ability to damage the host organism. Storage of melanin at the site of damage also prevents further loss of hemolymph.

Long-term or overproduce of substances arising during a PO cascade can lead to tissue damage and cell death at the site of the reaction. For this reason, these reactions are strictly regulated.

Notes and References

1. Amparyup P, Charoensapsri W, Tassanakajon A . Prophenoloxidase system and its role in shrimp immune responses against major pathogens . Fish & Shellfish Immunology . 34 . 4 . 990–1001 . April 2013 . 22960099 . 10.1016/j.fsi.2012.08.019 .
2. Cerenius L, Söderhäll K . The prophenoloxidase-activating system in invertebrates . Immunological Reviews . 198 . 116–26 . April 2004 . 15199959 . 10.1111/j.0105-2896.2004.00116.x . 10614298 .
3. Sugumaran M, Nellaiappan K, Valivittan K . A new mechanism for the control of phenoloxidase activity: inhibition and complex formation with quinone isomerase . Archives of Biochemistry and Biophysics . 379 . 2 . 252–60 . July 2000 . 10898942 . 10.1006/abbi.2000.1884 .
4. Zhao P, Li J, Wang Y, Jiang H . Broad-spectrum antimicrobial activity of the reactive compounds generated in vitro by Manduca sexta phenoloxidase . Insect Biochemistry and Molecular Biology . 37 . 9 . 952–9 . September 2007 . 17681234 . 2047599 . 10.1016/j.ibmb.2007.05.001 .
5. Nappi AJ, Christensen BM . Melanogenesis and associated cytotoxic reactions: applications to insect innate immunity . Insect Biochemistry and Molecular Biology . 35 . 5 . 443–59 . May 2005 . 15804578 . 10.1016/j.ibmb.2005.01.014 .
6. Söderhäll K, Cerenius L . Role of the prophenoloxidase-activating system in invertebrate immunity . Current Opinion in Immunology . 10 . 1 . 23–8 . February 1998 . 9523106 . 10.1016/S0952-7915(98)80026-5 .
7. Marmaras VJ, Charalambidis ND, Zervas CG . Immune response in insects: the role of phenoloxidase in defense reactions in relation to melanization and sclerotization . Archives of Insect Biochemistry and Physiology . 31 . 2 . 119–33 . 1996 . 8580494 . 10.1002/(SICI)1520-6327(1996)31:2<119::AID-ARCH1>3.0.CO;2-V .