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Production and metabolism of platelet-activating factor by human bone marrow cells
F Dupuis1, F Rougier, F Trimoreau
1Laboratoire d'Hématologie Expérimentale, Faculté de Médecine, Limoges, France.
Abstract:
Platelet-activating factor (PAF) is a phospholipid mediator of inflammation present in the human bone marrow. Freshly isolated human mononuclear bone marrow cells and marrow stromal cell cultures produced PAF under calcium ionophore (2 microM) and LPS (10 micrograms/ml) stimulation. By contrast, M-CSF (1000 U/ml), GM-CSF (100 ng/ml), IL1, IL3, IL6 and stem cell factor (10 ng/ml) did not stimulate PAF production. Marrow stromal cells produced 50-fold more PAF than freshly isolated mononuclear marrow cells, suggesting that stromal cells might be the major source of the human marrow-derived PAF. Mononuclear marrow cells and stromal cell cultures metabolized PAF with 1-alkyl-2-acyl-glycerophosphocholine as the major metabolic product. PMSF and p-BPB decreased the catabolism of PAF by freshly isolated marrow cells, but not by stromal cell cultures. While stromal cells rather than haematopoietic progenitors might be a major source of the human bone-marrow-derived PAF, both cell types metabolize it, suggesting their putative role in the regulation of PAF concentration in the human bone marrow.
Insights
Human bone marrow stromal cells are a major source of platelet-activating factor (PAF), a key inflammation mediator. Both stromal and mononuclear cells metabolize PAF, suggesting a role in regulating its concentration in bone marrow.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- Platelet-activating factor (PAF) is a significant phospholipid mediator involved in inflammatory processes.
- PAF has been detected in human bone marrow, but its cellular source and regulation remain incompletely understood.
Purpose of the Study:
- To investigate the cellular sources of PAF production in human bone marrow.
- To determine the metabolic fate of PAF by human bone marrow cells.
- To explore the role of different cell types in regulating PAF concentration.
Main Methods:
- Human bone marrow mononuclear cells and marrow stromal cell cultures were stimulated with calcium ionophore and lipopolysaccharide (LPS).
- Production of PAF was quantified under various stimulation conditions.
- Metabolism of PAF was assessed, and major metabolic products were identified.
- The effect of protease inhibitors (PMSF, p-BPB) on PAF catabolism was evaluated.
Main Results:
- Marrow stromal cells produced significantly higher levels of PAF (50-fold) compared to freshly isolated mononuclear marrow cells.
- PAF production was stimulated by calcium ionophore and LPS, but not by M-CSF, GM-CSF, IL1, IL3, IL6, or stem cell factor.
- Both mononuclear and stromal cells metabolized PAF, with 1-alkyl-2-acyl-glycerophosphocholine identified as the primary metabolite.
- PMSF and p-BPB inhibited PAF catabolism in mononuclear cells but not in stromal cells.
Conclusions:
- Human bone marrow stromal cells are likely the predominant source of PAF in the bone marrow.
- Both hematopoietic progenitors (mononuclear cells) and stromal cells contribute to PAF metabolism.
- These findings suggest a dual role for bone marrow cells in both producing and regulating PAF levels, impacting inflammatory responses within the bone marrow microenvironment.