Enhancement of CD4+ T-cell-dependent interleukin-2 production in vitro by murine alveolar macrophages: the role of leukotriene B4.
Local tissue macrophages are known to play a key role in regulation of adaptive immune responses, often by inhibition of T-cell activation and proliferation. In this study, we compare the influence of alveolar and peritoneal macrophages on T-cell-dependent interleukin-2 (IL-2) release. Alveolar macrophages, in contrast to peritoneal macrophages, enhance IL-2 release. Assay of a panel of potential macrophage-derived mediators indicated that activated alveolar macrophages stimulated greater release of IL-1 beta, tumour necrosis factor-alpha and, especially, leukotriene B4 (> 100 times) than activated peritoneal macrophages. Inhibition of prostaglandin synthesis by alveolar macrophages further enhanced the production of IL-2, while inhibition of leukotriene synthesis abolished the enhancement. The addition of exogenous prostaglandin E2 inhibited IL-2 release, while exogenous leukotriene B4 enhanced IL-2 release. When added simultaneously, the two compounds antagonized each other's activity. In conclusion, this study confirms that alveolar macrophages enhance IL-2 secretion, and suggests that this enhancement may be due at least in part to the very high rates of production of leukotriene B4. The overall influence of macrophage populations on T cells in vivo will reflect the complex balance between the multiple mediators produced within the local tissue microenvironment.
Marcinkiewicz
J
J
Department of Immunology, Jagiellonian University Medical College, Krakow, Poland.
Grabowska
A
A
Bryniarski
K
K
Chain
B M
BM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis*; D007975:Leukotriene B4 / Q000276:immunology* / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010853:Picryl Chloride / Q000276:immunology
D007376:Interleukin-2; D007975:Leukotriene B4; D015232:Dinoprostone; D010853:Picryl Chloride