1847170

pubmed:Citation

5

Platelet-activating factor is a potent mediator of the inflammatory response. Studies of the actions of platelet-activating factor have centered mainly around neutrophils, monocytes, and platelets. In this report we begin to uncover the influence of platelet-activating factor on B lymphocytes. Employing the EBV-transformed human B cell line SKW6.4, we demonstrate that platelet-activating factor significantly alters membrane phospholipid metabolism indicated by the incorporation of 32P into phosphatidylcholine, phosphatidylinositol, and phosphatidic acid but not significantly into phosphatidylethanolamine at concentrations ranging from 10(-9) to 10(-6) M. The inactive precursor, lyso-platelet-activating factor, at a concentration as high as 10(-7) M had no effect on any of the membrane phospholipids. We also show that platelet-activating factor from 10(-12) to 10(-6) M induced rapid and significant elevation in intracellular calcium levels, whereas lyso-platelet-activating factor was again ineffective. We further demonstrate the impact of platelet-activating factor binding to B cells by measuring platelet-activating factor induced arachidonic acid release and 5-hydroxyeicosatetraenoic acid production. Moreover, platelet-activating factor was capable of inducing transcription of the nuclear proto-oncogenes c-fos and c-jun. Finally we explored the possible role of 5-hydroxyeicosatetraenoic acid as a regulator of arachidonic acid liberation demonstrating that endogenous 5-lipoxygenase activity modulates platelet-activating factor induced arachidonic acid release perhaps acting at the level of phospholipase A2. In summary, platelet-activating factor is shown here to have a direct and profound effect on a pure B cell line.

eng

AIM

MEDLINE

0022-1767

Print

146

NLM

1642-8

pubmed-meshheading:1847170-Arachidonic Acid, pubmed-meshheading:1847170-Arachidonic Acids, pubmed-meshheading:1847170-B-Lymphocytes, pubmed-meshheading:1847170-Calcium, pubmed-meshheading:1847170-Cell Line, Transformed, pubmed-meshheading:1847170-DNA-Binding Proteins, pubmed-meshheading:1847170-Eicosanoids, pubmed-meshheading:1847170-Gene Expression Regulation, pubmed-meshheading:1847170-Herpesvirus 4, Human, pubmed-meshheading:1847170-Humans, pubmed-meshheading:1847170-Hydroxyeicosatetraenoic Acids, pubmed-meshheading:1847170-Membrane Lipids, pubmed-meshheading:1847170-Phospholipids, pubmed-meshheading:1847170-Phosphorus Radioisotopes, pubmed-meshheading:1847170-Platelet Activating Factor, pubmed-meshheading:1847170-Proto-Oncogene Proteins, pubmed-meshheading:1847170-Proto-Oncogene Proteins c-fos, pubmed-meshheading:1847170-Proto-Oncogene Proteins c-jun, pubmed-meshheading:1847170-RNA, Messenger, pubmed-meshheading:1847170-Transcription Factors, pubmed-meshheading:1847170-Up-Regulation

Platelet-activating factor induces phospholipid turnover, calcium flux, arachidonic acid liberation, eicosanoid generation, and oncogene expression in a human B cell line.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't