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Published on: December 23, 2010
Arachidonic acid and leukotriene B4 induce aggregation of human peripheral blood mononuclear leucocytes in vitro
Abstract:
Peripheral human blood mononuclear leucocytes (MNL) aggregated in response to arachidonic acid (AA) in vitro. This phenomenon was similar to that already described for polymorphonuclear cells (PMN). The effect of AA was concentration-dependent and was shared only by the structurally related di-homo-gamma-linolenic acid among the other fatty acids tested. A number of agents able to induce platelet aggregation such as ADP, collagen, serotonin and a stable prostaglandin analogue all failed to stimulate MNL or PMN aggregation. Inhibitors of cyclo-oxygenase activity such as acetylsalicylic acid and indomethacin not only did not prevent AA-induced aggregation, but even potentiated it. In contrast, both nordihydroguaiaretic acid and BW 755C, two inhibitors of cyclo-oxygenase and lipoxygenase, strongly prevented MNL aggregation. Thus AA seems to aggregate MNL through the mediation of lipoxygenase products. This is supported by the observation that leukotriene B4 (LTB4) also induced MNL aggregation. When highly purified lymphocyte and monocyte preparations were assessed separately, the latter responded to AA similarly to mixed MNL whereas lymphocyte aggregation was inconsistent, small and reversible even at high concentrations of AA. Although the pathophysiological significance of the MNL aggregation described here is still obscure, assembly of these cells--particularly monocytes--at the site of injury might be a crucial event.
Insights
Arachidonic acid (AA) causes human peripheral blood mononuclear leukocytes (MNL) to aggregate, similar to polymorphonuclear cells (PMN). This aggregation is mediated by lipoxygenase products, not cyclo-oxygenase pathways.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Peripheral human blood mononuclear leukocytes (MNL) exhibit aggregation in response to arachidonic acid (AA) in vitro.
- This aggregation phenomenon is comparable to that observed in polymorphonuclear cells (PMN).
Purpose of the Study:
- To investigate the mechanism of arachidonic acid (AA)-induced aggregation in human peripheral blood mononuclear leukocytes (MNL).
- To determine the role of lipoxygenase and cyclo-oxygenase pathways in MNL aggregation.
Main Methods:
- Assessing the concentration-dependent aggregation of MNL induced by arachidonic acid (AA) and related fatty acids.
- Evaluating the effects of various aggregation inducers (ADP, collagen, serotonin, prostaglandin analogue) on MNL and PMN.
- Testing the impact of cyclo-oxygenase inhibitors (acetylsalicylic acid, indomethacin) and dual cyclo-oxygenase/lipoxygenase inhibitors (nordihydroguaiaretic acid, BW 755C) on AA-induced MNL aggregation.
- Investigating the aggregation response of purified lymphocyte and monocyte preparations to AA and leukotriene B4 (LTB4).
Main Results:
- Arachidonic acid (AA) induced concentration-dependent aggregation of MNL, a property shared only by di-homo-gamma-linolenic acid among tested fatty acids.
- Agents that induce platelet aggregation did not stimulate MNL or PMN aggregation.
- Inhibitors of cyclo-oxygenase activity potentiated AA-induced aggregation, while dual inhibitors of cyclo-oxygenase and lipoxygenase strongly prevented it.
- Leukotriene B4 (LTB4) also induced MNL aggregation, supporting the role of lipoxygenase products.
- Monocytes responded robustly to AA, while lymphocyte aggregation was inconsistent and reversible.
Conclusions:
- Arachidonic acid (AA) appears to aggregate human peripheral blood mononuclear leukocytes (MNL) primarily through the mediation of lipoxygenase products.
- The findings suggest that monocyte assembly at injury sites, potentially mediated by AA-induced aggregation, could be a significant pathophysiological event.
