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Increased expression of cytosolic phospholipase A2, 5-lipoxygenase and 5-lipoxygenase-activating protein in rat peritoneal macrophages during ovalbumin-induced sensitization (2001)

Escoubet-Lozach, L. ; M'Rini, C. ; Rey, A. ; [et al.]

Oxford, UK : Blackwell Science, Ltd

Clinical & experimental allergy 31 (2001), S. 0

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ISSN: 1365-2222

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Medicine

Notes: Background Macrophages are involved in immediate hypersensitivity reactions by their ability to release leukotrienes involved in the symptomatology of allergy. To date it is unknown whether this ability to secrete leukotrienes has been favoured by modifications, occurring during the sensitization phase, of the enzymes involved in leukotriene metabolism.Objective We used ovalbumin-sensitized rats to study the expression of cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) in peritoneal macrophages during active sensitization. We compared basal and challenged (PMA, A23187 and allergen) arachidonic acid (AA) metabolism of macrophages from control (cPM) and sensitized (sPM) rats. Then we tested, in cultured cPM, whether IL-4, the predominant cytokine of sensitization process, could reproduce the enzymatic modifications occurring in macrophages during sensitization.Methods cPLA2, 5-LO and FLAP expression was assessed by Western blotting. The arachidonic acid (AA) metabolism study was performed after incorporation of tritiated AA in macrophages and analysis of secreted tritiated eicosanoids.Results Ovalbumin-sensitization of rats increased cPLA2, 5-LO and FLAP expression in peritoneal macrophages. These increased expressions were not paralleled by modifications of basal and PMA- or A23187-stimulated AA metabolism of sPM. However, when macrophages encountered the specific allergen for a second time, sPM secreted higher levels of leukotrienes than cPM. IL-4 induced FLAP expression in cPM but had no effect on cPLA2 and 5-LO expression.Conclusion Active sensitization of rats induces an increase, in peritoneal macrophages, of the enzymes involved in leukotriene metabolism. The increased leukotriene secretion of sPM in response to ovalbumin challenge may be favoured by this increased expression of cPLA2, 5-LO and FLAP that, however, is not able to lead to modifications of macrophage AA metabolism in any circumstance. Our results also suggest that IL-4 is not the major element originating the enzymatic modification induced by sensitization in peritoneal macrophages.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1046/j.1365-2222.2001.01121.x

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Immunocytochemical Characterization of Lung Macrophage Surface Phenotypes and Expression of Cytokines in Acute Experimental Silicosis in Mice (1998)

Orfila, C. ; Lepert, J. C. ; Gossart, S. ; [et al.]

Springer

Journal of molecular histology 30 (1998), S. 857-867

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ISSN: 1573-6865

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Abstract The expression of the surface phenotypical profile and the cytokines TNF-α and IL-1β from murine lung macrophages was studied in parenchymal lung tissue and bronchoalveolar fluid of mice, over a 2-week period, following a single intratracheal instillation of silica. The acute inflammatory reaction, confirmed by a significant augmentation of four times the control values of the number of macrophages recovered by lavage from experimental animals, was followed by organized granulomas in the interstitium. The immunohistochemical analysis of lung tissue sections after silica instillation demonstrated the increased alveolar and interstitial tissue expression of all surface antigens and cytokines studied, mainly Mac-1, F4/80 antigens, TNF-α and IL-1β, which were occasionally observed in normal uninjected and saline-treated mice. These findings show that, after silica instillation, the expression of surface phenotypical markers of lung macrophages increased, and this change was concomitantly associated with an increased expression of the cytokines TNF-α and IL-1β. These changes support the conclusion that an influx of the newly recruited and activated macrophage population, with a different phenotype, is induced by treatment during inflammation. The populational changes involve difference in functional activity and enhance TNF-α and IL-1β expression. These cytokines, produced in the silicosis-induced inflammatory process, are associated with the development of fibrosis and may contribute to disease severity. © 1998 Chapman & Hall