Related Experiment Videos
Lipoxygenase products and the polymorphonuclear leucocyte
Abstract:
Polymorphonuclear leucocytes (PMNs), when exposed to the calcium ionophore A23178, release into the supernatant a substance that causes the aggregation and chemokinesis of fresh PMN suspensions. Release of these activities is inhibited by preincubation with drugs known to inhibit lipoxygenase pathways of arachidonic acid metabolism but is unaffected by cyclooxygenase inhibitors. The substance responsible for these activities has been identified as leukotriene B and this compound has been shown to be a potent chemokinetic and aggregatory agent for PMNs over the range 10 pg to 5 ng ml-1.
Insights
Polymorphonuclear leucocytes (PMNs) release a substance that aggregates and drives movement in fresh PMNs. This substance was identified as leukotriene B, a potent agent for PMN aggregation and chemokinesis.
Area of Science:
- Immunology
- Biochemistry
- Cell Biology
Background:
- Polymorphonuclear leucocytes (PMNs) play a crucial role in inflammatory responses.
- Arachidonic acid metabolism pathways, including lipoxygenase and cyclooxygenase, are involved in inflammatory mediator production.
Purpose of the Study:
- To identify the substance released by PMNs that affects PMN aggregation and chemokinesis.
- To investigate the role of arachidonic acid metabolism in the release of this substance.
Main Methods:
- PMNs were stimulated with the calcium ionophore A23178.
- Supernatants were collected and tested for their effects on fresh PMN suspensions.
- The effects of lipoxygenase and cyclooxygenase inhibitors on the release of these activities were assessed.
- The active substance was purified and identified.
Main Results:
- PMN stimulation with A23178 induced the release of a substance causing PMN aggregation and chemokinesis.
- Inhibition of lipoxygenase pathways, but not cyclooxygenase pathways, blocked the release of these activities.
- The substance responsible was identified as leukotriene B (LTB4).
- Leukotriene B4 demonstrated potent chemokinetic and aggregatory effects on PMNs within a specific concentration range.
Conclusions:
- Leukotriene B4 is a key mediator released by PMNs that enhances inflammatory cell recruitment and activity.
- The lipoxygenase pathway is critical for the synthesis of LTB4, highlighting its importance in PMN-mediated inflammation.