|
Mediator |
Consequences of Overproduction |
|
Reactive oxidant species:
O2-, H2O2, HOCl, OH’ |
Damage cellular lipids, proteins and DNA. Implicated in cancer, cardiovascular disease, atherosclerosis, neurodegenerative diseases and others [9]. |
|
Nitric Oxide Synthase-derived Nitrogen Intermediates & Peroxynitrite |
Peroxynitrite implicated in cardio-vascular disease, neurodegeneration, diabetes etc. [123]. |
|
Proteases e.g. serine proteases in the azurophilic granules: Cathepsin G, elastase, proteinase 3
Matrix metalloproteinases e.g. MMP-8 & MMP-9 |
Degrades matrix proteins such as elastin; implicated in emphysema, chronic bronchitis and cystic fibrosis [124].
Cause matrix breakdown in COPD, ARDS, sarcoidosis, and tuberculosis etc [125]. |
|
Lipid mediators: LTB4, LTC4,LTD4, Platelet Activating Factor (PAF), PGE2 |
Overproduction of LTB4 associated with leukocyte recruitment is involved in the pathogenesis of inflammatory diseases such as bronchial asthma, rheumatoid arthritis, atherosclerosis, and inflammatory bowel disease [126]. LTC4, LTD4 play a role in asthma [127]. |
|
Cytokines: Pro-inflammatory cytokines e.g. IL-1, IL-6, TNF, IL-12, & anti-inflammatory cytokines, IL-1 receptor antagonist (IL-1Ra), IL-10 |
Overproduction of proinflammatory cytokines such as TNF may be involved in septic shock, autoimmunity & inflammatory diseases [128]. |
|
Chemokines: IL-8, Macrophage Inflammatory Protein(MIP)-1a & b, monocyte chemotactic protein-1 (MCP-1) |
Overproduction of chemokines such as IL-8 may be involved in inflammatory conditions, e.g. COPD, ARDS [129-130]. |
Abbreviations: LT: Leukotriene; PGE2: Prostaglandin E2; COPD: Chronic Obstructive Pulmonary Disease; ARDS: Acute Respiratory Distress Syndrome |
