Role of Phagocytes

We have already stressed the potential importance of lipid-rich membranes in the skin as potential targets for ROS-induced damage and ageing of human skin is morphologically identical to changes found by peroxidative processes (Serri et al., 1977). The involvement of AA metabolites in skin disease, and in particular psoriasis, has been the subject of much recent interest. Studies have included topical and intradermal administrations of AA metabolites, and assay of such products in clinical specimens. Results show that concentration of AA, 12-hydroxy-eicosatetraenoic acid (12-HETE), PG and leu-kotrienes are increased in psoriatic lesions (Hammarstrom etal., 1975 Camp etal., 1983 Brain etal., 1984 Duell et al., 1988) and also that full-thickness epidermis from normal and diseased skin has the enzymatic capacity to convert AA to some of the same metabolites (Hammarstrom etal., 1975, 1979 Camp etal., 1983 Brain etal., 1984 Ziboh et al., 1984 DueU et al., 1988). The biological effect of both 12-HETE and leukotrienes was confirmed by both topical application and intradermal injection, which caused epidermal inflammation and 

Skin inflammation is invariably associated with itching and lesions tend to be traumatized by scratching. This causes bleeding into tissues leading to haemoglobin 

In mouse models of skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), there is a close association between elevated XO activity in the epidermis and hyperplasia (Pence and Reiners, 1987). This association is also seen in psoriasis patients (Eisen and Seegmiller, 1961 Zimmer and Demis, 1966 Kizaki et al., 1977). In the study by Kizaki etal. (1977), the epidermis was increased about five-fold in comparison to normal. It is not known whether XO-derived ROS have any role in psoriatic epidermal hyperproliferation but low levels of hydrogen peroxide added to the culture medium are well known to induce skin fibroblast proliferation in vitro, an eflfect that is greatest at low passage numbers (Murrell et al., 1990). The generation of 

The radical nitric oxide (NO) has been shown to be a labile humoral substance causing vasodilatation by 

There have been recent studies on the importance of NO in modulating skin blood flow in both normal animals and in inflammatory models. Khan etiU. (1993), using laser-Doppler techniques, showed that the NOS inhibitor L-NAME inhibited rabbit ear blood flow. It was possible to do this chronically for up to 2 weeks using implanted osmotic pumps. Pons et id. (1993) also used laser Doppler to show that the vasodilator eflFect of LPS in rabbit skin, which mimics the efiect of Gram-negative bacteria, was likely to involve both i-NOS and IL-1. We have already discussed the damaging eflPects of neutrophils 

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Ultraviolet-induced Skin Inflammation 4.1 Role of Phagocytes... 

Weitzman, S.A. and Gordon, L.l. (1990). Inflammation and cancer role of phagocyte-generated oxidants in carcinogenesis. Blood 76, 655-663. 

Van Lent PLEM, Van De Hoek A, Van Den Bersselaar L, Spanjaards MFR, Van Rooijen N, Dijkstra CD, Van De Putte LBA, Van Den Berg WB (1993) In vivo role of phagocytic synovial lining cells in onset of experimental arthritis. Am J Pathol 143 1226... 

Elbim C, Pillet S, Prevost MIL, Preira A, Girard PM, Rogine N, Flakim J, Israel N, Gougerot-Pocidalo MA The role of phagocytes in FllV-related oxidative stress. J Clin Virol 2001 20 99-109. 

This list indicates the important role of phagocytes and, in particular, the role of AM. However, recognition and interaction of phagocytes with deposited particles depends not only on contact, adherence, and binding by cell membrane receptors and energy-consuming activation and internalization, but also on the physicochemical properties of the particles. These factors have been excellently... 

Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M (1986) The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233(4760) 215-219 Glaser R, Kiecolt-Glaser JK (2005) Stress-induced immune dysfunction Implications for health. Nat Rev Immunol 5(3) 243-251... 

Metchnikoff (1883) recognized the role of cell types (phagocytes) which were responsible for the engulfinent and digestion of microorganisms. They are a major line of defence against microbes that breach the initial barriers described above. Two types of phagocytic cells are found in the blood, both of which are derived from the totipotent bone marrow stem cell. 

In addition to the well-characterized role of iron in catalysing redox interactions, other metallic contaminants, for example, nickel, may also contribute. In vivo toxicity studies have demonstrated the capacity of nickel particulate compounds to induce tumours following intraperitoneal injection (Pott etal., 1987). Such activity is proportional to their phagocytic uptake, and to the associated respiratory burst and generation of PMN-derived reactive oxygen metabolites (ROMs), a proposed pathogenic mechanism (Evans et al., 1992a). 

The role of microtubules in secretion is more clearly defined. Colchicine and vinblastine inhibit secretion, even in cytochalasin-B-treated cells, and D2O (which promotes tubulin assembly) enhances secretion in cytochalasin-treated cells. Microtubules may also be necessary for the translocation of phagocytic vesicles from the neutrophil periphery into the central region of the cytoplasm. Drugs affecting microtubule assembly may inhibit particle-induced oxidase activation or else increase oxidase activation in response to soluble agents such as fMet-Leu-Phe. 

Garland, L. G. (1992). New pathways of phagocyte activation The coupling of receptor-linked phospholipase D and the role of tyrosine kinase in primed neutrophils. FEMS Microbiol. Immunol. 105,229-38. 

Figure 1-14-7. Role of the HHP Shunt in Hepatocytes, Phagocytes, and Erythrocytes...

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