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. 1997 Jul;91(3):369–374. doi: 10.1046/j.1365-2567.1997.00266.x

Enhancement of CD4+ T-cell-dependent interleukin-2 production in vitro by murine alveolar macrophages: the role of leukotriene B4.

J Marcinkiewicz 1, A Grabowska 1, K Bryniarski 1, B M Chain 1
PMCID: PMC1364005  PMID: 9301525

Abstract

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.

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Selected References

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