[Frontiers in Bioscience, Landmark, 21, 839-855, January 1, 2016]

Pathophysiology of neutrophil-mediated extracellular redox reactions

Morana Jaganjac 1, 2 , Ana Cipak 2 , Rudolf Joerg Schaur 3 , Neven Zarkovic 2

1Anti Doping Lab Qatar, Toxicology and Multipurpose Department, Doha, Qatar, 2Laboratory for Oxidative Stress, Rudjer Boskovic Institute, HR-10002 Zagreb, Croatia, 3Institute of Molecular Biosciences, University of Graz, A-8010 Graz, Austria

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Oxidative burst of neutrophils
    3.1. ROS-induced lipid peroxidation
4. Antioxidative defense systems
5. Neutrophil induced oxidative damage of the extracellular matrix
6. Neutrophil mediated chronic diseases
    6.1. Atherosclerosis
    6.2. Inflammatory bowel disease
7. Ischemia reperfusion and transplantation injury
8. Carcinogenesis and spontaneous regression of cancer
    8.1. Unspecific lysis of tumor cells
    8.2. Neutrophils and tumor cells – intercellular redox signaling
9. Conclusions
10. Acknowledgements
11. References

1. ABSTRACT

Neutrophil granulocyte leukocytes (neutrophils) play fundamental role in the innate immune response. In the presence of adequate stimuli, neutrophils release excessive amount of reactive oxygen species (ROS) that may induce cell and tissue injury. Oxidative burst of neutrophils acts as a double-edged sword. It may contribute to the pathology of atherosclerosis and brain injury but is also necessary in resolving infections. Moreover, neutrophil-derived ROS may also have both a tumor promoting and tumor suppressing role. ROS have a specific activities and diffusion distance, which is related to their short lifetime. Therefore, the manner in which ROS will act depends on the cells targeted and the intra- and extracellular levels of individual ROS, which can further cause production of reactive aldehydes like 4-hydroxynonenal (HNE) that act as a second messengers of ROS. In this review we discuss the influence of neutrophil mediated extracellular redox reactions in ischemia reperfusion injury, transplant rejection and chronic diseases (atherosclerosis, inflammatory bowel diseases and cancer). At the end a brief overview of cellular mechanisms to maintain ROS homeostasis is given.

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Key Words: Neutrophils, Oxidative Burst, Chronic Diseases, Ischemia Reperfusion, Transplantation Injury, Cancer, Review

Send correspondence to: Morana Jaganjac, Senior Scientist, Toxicology and Multipurpose Department, Anti Doping Laboratory Qatar, Doha, State of Qatar; Tel: 97444132846, Fax: 97444132997, E-mail: mjaganjac@adlqatar.qa