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Lipoxygenase products and the polymorphonuclear leucocyte.
Agents and Actions
|December 1, 1980
Summary
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.