Dose-dependent agonist and antagonist effects of the platelet-activating factor analogue 1-palmitoyl-2-acetoyl-sn-glycero-3-phosphocholine on B lymphocytes.
BACKGROUND
Platelet activating-factor (PAF), an ether-linked phospholipid, is a potent activator of B lymphocyte cell lines. The related ester-linked phospholipid, 1-palmitoyl-2-acetoyl-sn-glycero-3-phosphocholine (PAGPC), is synthesized by tissues important in B-cell development.


OBJECTIVE
We examined whether PAGPC was capable of influencing immunoglobulin synthesis in B lymphocytes and compared its action with that of PAF. We also examined the interaction of the two mediators as agonists or competitive antagonists.


METHODS
Ramos, an IgM-secreting immature B-cell line that expresses PAF receptor, was used in these experiments. The effect of PAF, PAGPC, or both mediators together on IgM secretion and anti-IgM-mediated apoptosis was measured.


RESULTS
Both PAF and PAGPC stimulated IgM production in Ramos cells in a dose-dependent fashion, with PAGPC being approximately three logs less potent than PAF. The effect of both mediators was inhibited by specific PAF receptor antagonists. Preincubation with suboptimal concentrations of PAGPC inhibited the ability of PAF to increase IgM secretion by Ramos cells. Additionally, preincubation with low concentrations of PAGPC prevented PAF from rescuing Ramos cells from apoptosis induced by cross-linking the B-cell receptor with anti-IgM antibodies. PAGPC caused PAF receptor desensitization because displacement of bound PAGPC with high concentrations of bovine serum albumin did not reverse its PAF antagonist effect.


CONCLUSIONS
PAF and PAGPC are biologically active phospholipids, but PAF is approximately 1000 times more potent. At high concentrations, PAGPC acts similarly to PAF, whereas at lower concentrations, PAGPC acts as a functional PAF antagonist. Because it is secreted at sites of inflammation and allergic reactions, PAGPC may be an endogenous regulator of the effects of PAF.
Mazer
B D
BD
Division of Allergy and Clinical Immunology, Montreal Children's Hospital and the McGill University/Montreal Children's Hospital Research Institute, Canada.
Toledano
B
B
Saririan
M
M
Bastien
Y
Y
D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D007075:Immunoglobulin M; D010713:Phosphatidylcholines; D010972:Platelet Activating Factor; C043050:1-palmitoyl-2-acetyl-sn-glycero-3-phosphocholine