Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in humans and plays an important role in several essential biological processes such as bile acid conjugation, maintenance of calcium homeostasis, osmoregulation and membrane stabilization. Moreover, attenuation of apoptosis and its antioxidant activity seem to be crucial for the cytoprotective effects of taurine. Although these properties are not tissue specific, taurine reaches particularly high concentrations in tissues exposed to elevated levels of oxidants (e.g., inflammatory cells). It suggests that taurine may play an important role in inflammation associated with oxidative stress. Indeed, at the site of inflammation, taurine is known to react with and detoxify hypochlorous acid generated by the neutrophil myeloperoxidase (MPO)–halide system. This reaction results in the formation of less toxic taurine chloramine (TauCl). Both haloamines, TauCl and taurine bromamine (TauBr), the product of taurine reaction with hypobromous acid (HOBr), exert antimicrobial and anti-inflammatory properties. In contrast to a well-documented regulatory role of taurine and taurine haloamines (TauCl, TauBr) in acute inflammation, their role in the pathogenesis of inflammatory diseases is not clear. This review summarizes our current knowledge concerning the role of taurine, TauCl and TauBr in the pathogenesis of inflammatory diseases initiated or propagated by MPO-derived oxidants. The aim of this paper is to show links between inflammation, neutrophils, MPO, oxidative stress and taurine. We will discuss the possible contribution of taurine and taurine haloamines to the pathogenesis of inflammatory diseases, especially in the best studied example of rheumatoid arthritis.

The production of hypochlorous acid (HOCl) is a characteristic of granulocyte activation, a hallmark of the early phase of innate immune responses. In this study, we show that, in addition to its well-established role as a microbicide, HOCl can act as a natural adjuvant of adaptive immunity. HOCl enhances the T cell responses to the model Ag OVA, facilitating the processing and presentation of this protein via the class II MHC pathway. HOCl modification also enhances cross-presentation of the tumor Ag tyrosinase-related protein 2 via class I MHC. The adjuvant effects of HOCl are independent of TLR signaling. The enhanced presentation of HOCl-modified OVA is mediated via modification of the N-linked carbohydrate side chain rather than formation of protein aldehydes or chloramines. HOCl-modified OVA is taken up more efficiently by APCs and is degraded more efficiently by proteinases. Atomic force microscopy demonstrated that enhanced uptake is mediated via specific receptor binding, one candidate for which is the scavenger receptor lectin-like oxidized low-density lipoprotein receptor, which shows enhanced binding to chlorinated OVA. A function of HOCl is therefore to target glycoprotein Ags to scavenger receptors on the APC surface. This additional mechanism linking innate and adaptive immunity suggests novel strategies to enhance immunity to vaccines.

Taurine (Tau) is an exceptionally abundant free amino acid in the cytosol of inflammatory cells and especially in neutrophils. Taurine protects cells from self-destruction during processes that generate oxidants. The major function of Tau in leukocytes is to trap chlorinated oxidants (HOCl). Taurine reacts with HOCl to produce the long-lived compound taurine chloramine (TauCl). Previously, we have shown that other products of the neutrophil chlorinating system are able to modify functions of macrophages. In this study, we investigated in vitro the influence of TauCl on the generation of inflammatory mediators by activated macrophages. We have found that TauCl inhibited the generation of nitric oxide, prostaglandin E2, tumor necrosis factor alpha, and interleukin-6, but TauCl slightly enhanced the release of IL-1 alpha. The formation of nitrites by interferon-gamma-activated macrophages was inhibited by TauCl in a dose-dependent manner. Taurine chloramine also reduced the level of inducible nitric oxide synthase (iNOS) mRNA in macrophages, in a similar concentration-dependent manner. Although our experiments do not exclude a direct effect of TauCl on enzymatic activity of iNOS, the inhibition of iNOS expression seems to be the major mechanism responsible for suppression of NO formation. Finally, we discuss the biological role of TauCl in vivo. We suggest that at the site of inflammation TauCl works as a specific signaling molecule of activated neutrophils that coordinates the generation of inflammatory mediators in macrophages.

Nitric oxide (NO) plays a key role in mediating macrophage cytotoxicity towards different targets, including tumoral cells and intracellular pathogens. However, its role in macrophage immunoregulation is less well defined. In this study, we have investigated the effect of altering NO levels on the production by mouse macrophages of cytokines, and reactive oxygen intermediates as measured by luminol-dependent chemiluminescence. Our results demonstrate that NO can enhance the release of both tumor necrosis factor-alpha and interleukin-1 alpha, and chemiluminescence. Thus, in addition to acting as a powerful effector molecule in mediating cytotoxic activities of mouse macrophages, NO can play a role in enhancing the production of a variety of other inflammatory mediators, and thus can contribute both directly and indirectly to the immunopathology of macrophage-dependent inflammation.

Myeloperoxidase (MPO) is a major protein constituent of the primary granules of vertebrate neutrophils. It catalyses the hydrogen peroxide-mediated oxidation of halide ions to hypohalous acids, especially HOCl. These reactive oxygen species can participate in a variety of secondary reactions, leading to modifications of amino acids and many types of biological macromolecules. The classic paradigm views MPO as a component of the phagocyte oxygen-dependent intracellular microbicidal system, and thus an important arm of the effector phase of innate immune responses. However, the limited immunodeficiency associated with lack of MPO in mouse and human models has challenged this paradigm. In this review we examine more recent information on the interaction between MPO, its bioreactive reaction products, and targets within the inflammatory microenvironment. We propose that two assumptions of the current model may require revisiting. First, many important targets of MPO modification are extracellular, rather than present only within the phagolysosome, such as various components of neutrophil extracellular traps. Second, we suggest that the pro-inflammatory pathological role of MPO may be a particular feature of chronic inflammation. In the physiological setting of acute neutrophil-mediated inflammation MPO may also form part of a negative feedback loop which down-regulates inflammation, limits tissue damage, and facilitates the switch from innate to adaptive immunity. This different perspective on this well-studied enzyme may usefully inform further research into its function in health and disease.