Effects of monocyte‐lymphocyte interaction on the synthesis of leukotriene B₄

Abstract

Human monocytes in monolayers were challenged with the calcium ionophore A23187. Methanol trapping of the products in the cell-free supernatants, followed by analysis on HPLC and by ultraviolet spectroscopy, revealed the presence of two compounds, which exhibited a conjugated-triene spectrum and chromatographed with the compounds formed when synthetic leukotriene (LT) A, was added to warm acidified methanol. Furthermore, addition of purified LTA4 hydrolase to the cell-free supernatant of monocytes, stimulated with the ionophore A231 87, resulted in increased levels of LTB4. These results indicate that monocytes release LTA4 extracellularly after activation with the calcium ionophore.Incubation of monocytes together with monoclonal lymphocytic cells, of both B and T cell lineage, yielded increased levels of LTB4 whereas the non-enzymatic isomers of this compound, i. e. d6-trans-LTB4 and 12-epi-A6-trans-LTB,, declined. In addition, the sum of LTB4 and its non-enzymatically formed isomers increased in mixed cultures of monocytes and monoclonal lymphocytic cells as compared to monocytes alone.The present study indicates that activated monocytes release LTA,, which is converted into LTB4 by monoclonal lymphocytic cells. Furthermore, the increase of the total amounts of leukotrienes on incubation of monocytes with lymphocytic cells, suggests the presence of an additional mechanism leading to activation of the 5-lipoxygenase pathway in monocytes.Monocytes and macrophages possess 5-lipoxygenase activity and convert arachidonic acid to leukotrienes (LT) [l]. Leukotrienes influence several lymphocyte functions. Specific high-affinity binding sites for LTB4 have been described on these cells [18], and it has been reported that this compound induces natural killer and suppressor/cytotoxic cell activity [19]. LTB4 stimulates, in synergy with Blymphotrophic factors, expression of the activation-associated surface antigen CD23 on resting B lymphocytes [20]. Furthermore, initiation of DNA synthesis, cell growth and immunoglobulin production are enhanced in B cells by LTB, [20]. LTB, has also been reported to influence the formation and effects of several cytokines [21-241.The present study deals with the release of LTA, from activated monocytes and effects of monocytes monoclonal lymphoblastoid cell interactions on LTB4 synthesis.

Lymphocytes stimulate expression of 5-lipoxygenase and its activating protein in monocytes in vitro via granulocyte macrophage colony-stimulating factor and interleukin 3.

“…In addition, these authors found a more sustained increase in 5-lipoxygenase activity by 18 h, which was associated with the transcriptional activation of the 5-lipoxygenase gene, an increase in 5-lipoxygenase mRNA levels, and new 5-lipoxygenase protein synthesis. Studies by other investigators found that when human monocytes were coincubated with a monoclonal lymphocytic cell line for 10 min, there was an 80% increase in 5-lipoxygenase activity as reflected by leukotriene B 4 (LTB 4 ) release (22). Taken together, these studies have been limited either by the short time frame of the investigation or by reliance on cell lines.…”

On Radiation Damage to Normal Tissues and its Treatment: II. Anti-inflammatory drugs

“…Singling out the direct endothelial damage by radiation as a primary event is not supported either by the common knowledge that, whereas the microvasculature may be affected, the major blood vessels are mostly spared. Within the narrower scope of this part of the review which focuses on bioactive arachidonic acid dcrivatives, the possibility of blood vessel changes after irradiation being regulatory in character and caused at least in part indirectly (i.e., mediated by diffusible species also generated in nonvascular cells) is further supported by studies on heterologous cell-cell interactions in eicosanoid synthesis (66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79). There seems therefore to be insufficient reason for investigating only the endothelium and vascular smooth muscle cells in an attempt to unravel radiationinduced changes in blood vessels; responses of the intervening (i.e., other stromal and parenchymal) and bloodcirculating cells, as well as reciprocal cell interactions must be taken into account.…”

Asthma and leukotrienes: antileukotrienes as novel anti‐asthmatic drugs

“…Leukotriene C 4 can also be produced in the lung through interaction between different types of cells. Several lines of evidence suggest that stimulated leucocytes can release arachidonic acid or LTA 4 , which can be further metabolized by other surrounding cells (so-called transcellular metabolism) [74][75][76][77][78]. A [46,77,79].…”