Abstract
Platelet-activating factor,1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF), is a membrane phospholipid with immunomodulatory functions. We studied the influence of PAF on mitogen-stimulated proliferation of human peripheral blood mononuclear cells (PBMC), purified T cells and T cell subsets. High concentrations of PAF suppressed the proliferation of all cell populations studied (44% mean inhibition with 5 μM PAF and 78% inhibition with 10 μM PAF). In contrast, the deacetylated metabolite of PAF, lyso-PAF, had no effect on proliferation at micromolar concentrations. Lower, and presumably physiologically relevant, concentrations of PAF (10-14 to 10-8 M) stimulated a small increase in the proliferation of unfractionated T cells. When T cells were fractionated into CD4+ and CD8+ subsets, a difference in sensitivity to PAF was observed. PAF stimulated a modest, yet statistically significant, increase in the proliferation of CD4+ T cells at concentrations ranging from 10-14 to 10-10 M, while either having no effect or inhibiting the proliferation of CD8+ cells across the entire concentration range. Addition of indomethacin to the cultures further enhanced CD4+ proliferation, possible due to the blockade of PAF-induced PGE2 production by monocytes. The PAF receptor antagonist BN 52021 did not block the PAF effects in this system, and the PAF receptor antagonist SRI 63-675 caused a dose dependent inhibition of T cell subset proliferation. These findings suggest that while high concentrations of PAF suppress T cell proliferation, low concentrations selectively stimulate proliferation of the CD4+ subset, an effect which is partially counteracted by PAF-induced monocyte PGE2 production.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 175-184 |
| Number of pages | 10 |
| Journal | International Journal of Immunopharmacology |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| State | Published - 1990 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Pharmacology
Cite this
Control of human T cell proliferation by platelet-activating factor. / Behrens, Timothy W.; Goodwin, James.
In: International Journal of Immunopharmacology, Vol. 12, No. 2, 1990, p. 175-184.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Control of human T cell proliferation by platelet-activating factor
AU - Behrens, Timothy W.
AU - Goodwin, James
PY - 1990
Y1 - 1990
N2 - Platelet-activating factor,1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF), is a membrane phospholipid with immunomodulatory functions. We studied the influence of PAF on mitogen-stimulated proliferation of human peripheral blood mononuclear cells (PBMC), purified T cells and T cell subsets. High concentrations of PAF suppressed the proliferation of all cell populations studied (44% mean inhibition with 5 μM PAF and 78% inhibition with 10 μM PAF). In contrast, the deacetylated metabolite of PAF, lyso-PAF, had no effect on proliferation at micromolar concentrations. Lower, and presumably physiologically relevant, concentrations of PAF (10-14 to 10-8 M) stimulated a small increase in the proliferation of unfractionated T cells. When T cells were fractionated into CD4+ and CD8+ subsets, a difference in sensitivity to PAF was observed. PAF stimulated a modest, yet statistically significant, increase in the proliferation of CD4+ T cells at concentrations ranging from 10-14 to 10-10 M, while either having no effect or inhibiting the proliferation of CD8+ cells across the entire concentration range. Addition of indomethacin to the cultures further enhanced CD4+ proliferation, possible due to the blockade of PAF-induced PGE2 production by monocytes. The PAF receptor antagonist BN 52021 did not block the PAF effects in this system, and the PAF receptor antagonist SRI 63-675 caused a dose dependent inhibition of T cell subset proliferation. These findings suggest that while high concentrations of PAF suppress T cell proliferation, low concentrations selectively stimulate proliferation of the CD4+ subset, an effect which is partially counteracted by PAF-induced monocyte PGE2 production.
AB - Platelet-activating factor,1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF), is a membrane phospholipid with immunomodulatory functions. We studied the influence of PAF on mitogen-stimulated proliferation of human peripheral blood mononuclear cells (PBMC), purified T cells and T cell subsets. High concentrations of PAF suppressed the proliferation of all cell populations studied (44% mean inhibition with 5 μM PAF and 78% inhibition with 10 μM PAF). In contrast, the deacetylated metabolite of PAF, lyso-PAF, had no effect on proliferation at micromolar concentrations. Lower, and presumably physiologically relevant, concentrations of PAF (10-14 to 10-8 M) stimulated a small increase in the proliferation of unfractionated T cells. When T cells were fractionated into CD4+ and CD8+ subsets, a difference in sensitivity to PAF was observed. PAF stimulated a modest, yet statistically significant, increase in the proliferation of CD4+ T cells at concentrations ranging from 10-14 to 10-10 M, while either having no effect or inhibiting the proliferation of CD8+ cells across the entire concentration range. Addition of indomethacin to the cultures further enhanced CD4+ proliferation, possible due to the blockade of PAF-induced PGE2 production by monocytes. The PAF receptor antagonist BN 52021 did not block the PAF effects in this system, and the PAF receptor antagonist SRI 63-675 caused a dose dependent inhibition of T cell subset proliferation. These findings suggest that while high concentrations of PAF suppress T cell proliferation, low concentrations selectively stimulate proliferation of the CD4+ subset, an effect which is partially counteracted by PAF-induced monocyte PGE2 production.
UR - http://www.scopus.com/inward/record.url?scp=0025318657&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025318657&partnerID=8YFLogxK
U2 - 10.1016/0192-0561(90)90051-N
DO - 10.1016/0192-0561(90)90051-N
M3 - Article
VL - 12
SP - 175
EP - 184
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 2
ER -