B-cell activation and regulation of immunoglobulin synthesis by platelet activating factor.
Platelet activating factor (PAF) is a highly potent phospholipid mediator known to be active in many biologic systems. To date little is known of the effect of PAF on B lymphocytes. Using three immunoglobulin (Ig)-secreting B-lymphoblastoid lines, we have demonstrated that PAF can influence both early activation and late differentiation events. Following addition of 10(-7) to 10(-11) M PAF, but not the inactive metabolite lyso-PAF, all three cell lines demonstrated rapid, dose-dependent increases in free cytosolic Ca2+ concentrations ([Ca2+]i). The changes in [Ca2+]i resulted from release of intracellular stored Ca2+ as well as transmembrane Ca2+ uptake. In parallel PAF caused significant alterations in the kinetics of Ig secretion in the Ig-secreting lymphocyte lines. A 6-12-fold increase in Ig production was detectable after 24 h of stimulation with PAF, which was followed by a plateau over the next 48 h. All of these events were inhibited by the specific PAF antagonists Web2086 and CV3988. PAF antagonists themselves had a profound effect, diminishing Ig production by the B-cell lines by up to 90%. These data indicate that PAF may have an important immunomodulatory role in B lymphocytes.
Mazer
B D
BD
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80224.
Sawami
H
H
Franklin
R
R
Gelfand
E W
EW
D001381:Azepines / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D007294:Inositol / Q000378:metabolism; D008213:Lymphocyte Activation; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis*; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D011947:Receptors, Antigen, B-Cell; D014230:Triazoles; C052518:WEB 2086; D007294:Inositol; C037913:CV 3988; D002118:Calcium