Free radicals in inflammation: second messengers and mediators of tissue destruction

Abstract

In recent years it has become increasingly apparent that, in man, free radicals play a role in a variety of normal regulatory systems, the deregulation of which may play an important role in inflammation. As examples, we discuss the second messenger roles of: NO in the regulation of vascular tone, O2.- in fibroblast proliferation and H2O2 in the activation of transcription factors such as NF kappa B. Other control mechanisms, the physiological function of which may be perturbed in inflammation, include: the oxidative modification of low density lipoprotein, the oxidative inactivation of alpha-1-protease inhibitor, DNA damage/repair and heat shock protein synthesis. At sites of inflammation, increased free radical activity is associated with the activation of the neutrophil NADPH oxidase and/or the uncoupling of a variety of redox systems, including endothelial cell xanthine dehydrogenase. Although free radicals, thus produced, have the capacity to mediate tissue destruction, either alone or in concert with proteases, we argue that disturbances in the second messenger and regulatory activities of free radicals may also contribute significantly to the inflammatory process.

Peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin O

“…During infection, Mycobacterium leprae is faced with the host macrophagic environment, where low pH, low pO 2 , and high carbon dioxide (CO 2 ) levels, combined with reactive nitrogen and oxygen species including peroxynitrite (ONOO À /ONOOH) 1 and hydrogen peroxide (H 2 O 2 ), contribute to limit the growth of the bacilli and to host tissue damage [1][2][3][4][5][6][7][8][9][10]. Peroxynitrite is more reactive than its precursors nitrogen monoxide ( Å NO) and superoxide (O 2 ÅÀ ), promoting oxidative tissue injury by different mechanisms.…”

“…In fact, peroxynitrite reacts with bio-molecules either directly or after homolysis to nitrite radical ( Å NO 2 ) and hydroxyl radical ( Å OH). Furthermore, one of the main targets of peroxynitrite is thought to be CO 2 , present in millimolar concentrations in most fluids and tissues, apparently forming an adduct whose composition is believed to be ONOOC(O)O À (named 1-carboxylato-2-nitrosodioxidane or nitrosoperoxocarbonate), which is a stronger nitrating agent than ONOOH and is homolyzed to trioxocarbonate( Å 1 À ) (CO 3…”

Induction of urokinase-type plasminogen activator by the anthracycline antibiotic in human RC-K8 lymphoma and H69 lung-carcinoma cells

“…9 Hydrogen peroxide, in addition to IL-1 and LPS, 4 induces uPA expression in RC-K8 cells. 10 ROS, such as superoxide and hydrogen peroxide, are released from inflammatory cells during the inflammatory process, 11 and both IL-1 and TNF-␣ stimulate ROS production in human cells. 12 Current evidence suggests that these proinflammatory stimuli use ROS as signaling messengers to activate transcription factors, such as NF-B and AP-1, and induce expression of a number of genes.…”

A review of the use of pteridophytes for treating human ailments

“…The release of ROS from activated neutrophils and macrophages causes inflammation injury. Excessive production may lead to tissue injury by damaging macromolecules and lipid peroxidation of membranes (Winrow et al, 1993;Gutteridge, 1995). ROS inflammation stimulates the release of cytokines, such as interleukin-1, tumour necrosis factor-α, and interferon-α, which stimulate the production of extra neutrophils and macrophages.…”