The Role of Phagocytes in Immunity to Candida albicans

Body clearance of fungi such as Candida albicans involves phagocytosis by fixed tissue macrophages as well as infiltrating monocytes and neutrophils. Through phagocytosis, the fungi are confined and killed by the oxidative and non-oxidative anti-microbial systems. These include oxygen derived reactive species, generated from the activation of the NADPH oxidase complex and granule constituents. These same mechanisms are responsible for the damage to hyphal forms of C. albicans. Complement promotes phagocytosis, through their interaction with a series of complement receptors including the recently described complement receptor immunoglobulin. However, it is also evident that under other conditions, the killing of yeast and hyphal forms can occur in a complement-independent manner. Phagocytosis and killing of Candida is enhanced by the cytokine network, such as tumour necrosis factor and interferon gamma. Patients with primary immunodeficiency diseases who have phagocytic deficiencies, such as those with defects in the NADPH oxidase complex are predisposed to fungal infections, providing evidence for the critical role of phagocytes in anti-fungal immunity. Secondary immunodeficiencies can arise as a result of treatment with anti-cancer or other immunosuppressive drugs. These agents may also predispose patients to fungal infections due to their ability to compromise the anti-microbial activity of phagocytes

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Inhibition of Neutrophil Leukotriene B 4 Production by a Novel Synthetic N -3 Polyunsaturated Fatty Acid Analogue, β-Oxa 21:3 n -3

We recently reported the synthesis and anti-inflammatory properties of a novel long chain polyunsaturated fatty acid (PUFA) with an oxygen atom in the β-position, β-oxa-21:3 n-3 (Z,Z,Z)-(octadeca-9,12,15-trienyloxy) acetic acid). Our data, from studie

Polyunsaturated nitroalkanes and nitro-substituted fatty acids

Nitroalkanes 4 are readily prepared from naturally derived polyunsaturated fatty alcohols 1 via succesive conversion to the corresponding haloalkanes 2 and 3, and reaction with silver nitrite. Reaction of nitroalkanes 4a,b with methyl acrylate, followed by ester hydrolysis, affords nitro-substituted fatty acids 6a,b and 8a,b. Oxidation of alcohols 1a,b gives the corresponding aldehydes 9a,b, which react by Henry condensation with nitromethane to give β-hydroxynitroalkanes 10a,b

A novel long chain polyunsaturated fatty acid, β-oxa 21:3 n -3, inhibits T lymphocyte proliferation, cytokine production, delayed-type hypersensitivity, and carrageenan-induced paw reaction and selectively targets intracellular signals

A novel polyunsaturated fatty acid (PUFA) β-oxa 21:3n-3, containing an oxygen atom in the β position, was chemically synthesized, and found to have more selective biological activity than the n-3 PUFA, docosahexaenoic acid (22:6n-3) on cells of the imm

A novel [beta]-oxa polyunsaturated fatty acid downregulates the activation of the I[kappa]B kinase/nuclear factor [kappa]B pathway, inhibits expression of endothelial cell adhesion molecules, and depresses inflammation

Several novel polyunsaturated fatty acids (PUFAs) that contain either an oxygen or sulfur atom in the β-position were found to exhibit more selective antiinflammatory properties than their natural PUFA counterparts. One of these, β-oxa-23:4n-6, unlike

Stimulation of p38 phosphorylation and activity by arachidonic acid in HeLa cells, HL60 promyelocytic leukemic cells, and human neutrophils. Evidence for cell type-specific activation of mitogen-activated protein kinases

Although it is well appreciated that arachidonic acid, a second messenger molecule that is released by ligand-stimulated phospholipase A2, stimulates a wide range of cell types, the mechanisms that mediate the actions of arachidonic acid are still poorly understood. We now report that arachidonic acid stimulated the appearance of dual-phosphorylated (active) p38 mitogen-activated protein kinase as detected by Western blotting in HeLa cells, HL60 cells, human neutrophils, and human umbilical vein endothelial cells but not Jurkat cells. An increase in p38 kinase activity caused by arachidonic acid was also observed. Further studies with neutrophils show that the stimulation of p38 dual phosphorylation by arachidonic acid was transient, peaking at 5 min, and was concentration-dependent. The effect of arachidonic acid was not affected by either nordihydroguaiaretic acid, an inhibitor of the 5-, 12-, and 15-lipoxygenases or by indomethacin, an inhibitor of cyclooxygenase. Arachidonic acid also stimulated the phosphorylation and/or activity of the extracellular signal-regulated protein kinase and of c-jun N-terminal kinase in a cell-type-specific manner. An examination of the mechanisms through which arachidonic acid stimulated the phosphorylation/activity of p38 and extracellular signal-regulated protein kinase in neutrophils revealed an involvement of protein kinase C. Thus, arachidonic acid stimulated the translocation of protein kinase C alpha, betaI, and betaII to a particulate fraction, and the effects of arachidonic acid on mitogen-activated protein kinase phosphorylation/activity were partially inhibited by GF109203X, an inhibitor of protein kinase C. This study is the first to demonstrate that a polyunsaturated fatty acid causes the dual phosphorylation and activation of p38.Charles S. T. Hii, Zhi H. Huang, Andrea Bilney, Maurizio Costabile, Andrew W. Murray, Deborah A. Rathjen, Channing J Der and Antonio Ferrant