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Synthesis and release of platelet-activating factor by stimulated human mononuclear phagocytes
M R Elstad1, S M Prescott, T M McIntyre
1Nora Eccles Harrison Cardiovascular Research and Training Institute, Salt Lake City, UT 84112.
Abstract:
Platelet-activating factor (PAF) is a potent phospholipid mediator that may participate in inflammatory responses by virtue of its ability to activate platelets, leukocytes, and vascular cells. We examined the synthesis and release of PAF by human peripheral blood monocytes (PBM) isolated by countercurrent elutriation. PAF was produced after stimulation by calcium ionophore A23187 (IoA), opsonized zymosan (OpsZ), and PMA with a relative order of potency IoA much greater than OpsZ greater than PMA. The portion of PAF subsequently released from the cell was dependent on the specific agonist, the time of incubation, and the presence of albumin. Under optimal conditions, PBM released 67, 49 and 32% of the total PAF produced in response to IoA, OpsZ, and PMA, respectively. Changes in PAF metabolism were observed in PBM that were examined after short term adherence or differentiation into macrophages. Adherent PBM accumulated and released less PAF than suspended monocytes, and monocyte-derived macrophages produced less PAF than the parent PBM. The ability of monocytes to release significant amounts of newly synthesized PAF from the cell is unusual among human cell types, which in general retain the vast majority of the lipid, and may be of particular pathophysiologic importance.
Insights
Human monocytes release significant amounts of newly synthesized Platelet-Activating Factor (PAF) when stimulated. This release, unlike in other cells, may be important in inflammatory diseases.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Platelet-Activating Factor (PAF) is a potent phospholipid mediator involved in inflammatory responses.
- PAF activates platelets, leukocytes, and vascular cells, contributing to inflammation.
Purpose of the Study:
- To investigate the synthesis and release of PAF by human peripheral blood monocytes (PBM).
- To explore how PAF metabolism changes in adherent PBM and monocyte-derived macrophages.
Main Methods:
- Human peripheral blood monocytes (PBM) were isolated using countercurrent elutriation.
- PAF production and release were measured after stimulation with calcium ionophore A23187 (IoA), opsonized zymosan (OpsZ), and PMA.
- PAF metabolism was assessed in adherent PBM and differentiated macrophages.
Main Results:
- PBM synthesized and released PAF in response to IoA, OpsZ, and PMA, with potency order IoA > OpsZ > PMA.
- The percentage of released PAF varied with agonist, incubation time, and albumin presence, reaching up to 67% with IoA.
- Adherent PBM and monocyte-derived macrophages showed reduced PAF accumulation and release compared to suspended monocytes.
Conclusions:
- Human monocytes possess a unique ability to release substantial amounts of newly synthesized PAF.
- This monocyte-specific PAF release mechanism may hold significant pathophysiological importance in inflammatory conditions.