Autocrine stimulation of B lymphocytes by a platelet-activating factor receptor agonist, 1-palmitoyl-2-acetoyl-sn-glycero-3-phosphocholine

A. Tordai, R. A. Franklin, C. Johnson, B. D. Mazer, K. L. Clay, E. W. Gelfand

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Based on previous data which demonstrated the ability of platelet- activating factor (PAF) antagonists to inhibit constitutive immunoglobulin synthesis in B-lymphoblastoid cell lines, we determined the capacity of these cells to synthesize PAF or 1-palmitoyl-2-acetyl-sn-glycero-phosphocholine (PAGPC), an acyl-PAF identified in various cell types. In two B- lymphoblastoid cell lines (LA350 and HSCE-), significant amounts of production of PAGPC were detected, whereas the amount of PAF was below the level of detection in our system. The biologic effects of PAGPC were examined in these cells, both of which have well-characterized PAF receptors. PAGPC induced a concentration-dependent increase in intracellular Ca2+ concentrations and activation of MAP-2 kinase (as detected by immunoblotting and measurements of kinase activity) in these cells. The kinetics and magnitude of these responses were similar to those induced by PAF, and they were inhibited by Web 2086, a PAFR antagonist. Phosphatidylcholine, which differs from PAGPC in that it contains a long fatty acid residue at position 2, did not induce any of these responses. A mutual cross-desensitization of the B lymphoblasts between PAGPC and PAF was observed for Ca2+ mobilization. To induce maximal cell stimulation, approximately 600-fold higher concentrations of PAGPC than of PAF were needed. Because the two B- lymphoblastoid cell lines synthesized significant amounts of PAGPC, this phospholipid may participate in an autocrine stimulation pathway in B cells. Furthermore, the data indicate that PAGPC is an agonist for the PAFR in B lymphoblasts and that the ether linkage in the PAF molecule is not an absolute requirement for activity, although it increases the potency of the ligand.

Original languageEnglish
Pages (from-to)566-573
Number of pages8
JournalJournal of Immunology
Volume152
Issue number2
Publication statusPublished - Jan 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Autocrine stimulation of B lymphocytes by a platelet-activating factor receptor agonist, 1-palmitoyl-2-acetoyl-sn-glycero-3-phosphocholine'. Together they form a unique fingerprint.

  • Cite this