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Monocytes regulate osteoclast-activating factor production by releasing prostaglandins
The Journal of Experimental Medicine
|August 1, 1979
Summary
Activated lymphocytes produce osteoclast-activating factor (OAF), but require monocyte-derived prostaglandins for OAF release, impacting bone resorption in diseases.
Area of Science:
- Immunology
- Cell Biology
- Bone Physiology
Background:
- Osteoclast-activating factor (OAF) stimulates bone resorption.
- OAF release by peripheral blood mononuclear cells requires both lymphocytes and monocytes.
- The specific roles of lymphocytes and monocytes in OAF production were unclear.
Purpose of the Study:
- To investigate the relationship between lymphocytes and monocytes in osteoclast-activating factor (OAF) production.
- To elucidate the mechanisms regulating OAF release and its impact on bone resorption.
Main Methods:
- Assessed OAF biological activity using a 45Ca release bioassay from fetal rodent long bones.
- Utilized enriched lymphocyte populations depleted of monocytes.
- Investigated the effect of conditioned media from adherent cells (monocytes) and prostaglandins (PGE1, PGE2) on OAF release.
Main Results:
- Enriched lymphocytes lacking monocytes did not release OAF upon stimulation with phytohemagglutinin (PHA).
- Conditioned media from monocytes, but not from indomethacin-treated monocytes, enabled OAF release by lymphocytes.
- Exogenous prostaglandins (PGE1, PGE2) restored OAF release in lymphocyte-enriched populations.
Conclusions:
- Activated lymphocytes are the source of osteoclast-activating factor (OAF).
- Monocyte-produced prostaglandins are essential for OAF production by activated lymphocytes.
- Monocyte prostaglandins influence bone resorption indirectly via OAF regulation and directly via osteoclast activation, relevant to bone-destructive diseases.