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Platelet-activating factor induces phospholipid turnover, calcium flux, arachidonic acid liberation, eicosanoid generation, and oncogene expression in a human B cell line.
J Immunol. 1991 Mar 01; 146(5):1642-8.JI

Abstract

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.

Authors+Show Affiliations

Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

1847170

Citation

Schulam, P G., et al. "Platelet-activating Factor Induces Phospholipid Turnover, Calcium Flux, Arachidonic Acid Liberation, Eicosanoid Generation, and Oncogene Expression in a Human B Cell Line." Journal of Immunology (Baltimore, Md. : 1950), vol. 146, no. 5, 1991, pp. 1642-8.
Schulam PG, Kuruvilla A, Putcha G, et al. Platelet-activating factor induces phospholipid turnover, calcium flux, arachidonic acid liberation, eicosanoid generation, and oncogene expression in a human B cell line. J Immunol. 1991;146(5):1642-8.
Schulam, P. G., Kuruvilla, A., Putcha, G., Mangus, L., Franklin-Johnson, J., & Shearer, W. T. (1991). Platelet-activating factor induces phospholipid turnover, calcium flux, arachidonic acid liberation, eicosanoid generation, and oncogene expression in a human B cell line. Journal of Immunology (Baltimore, Md. : 1950), 146(5), 1642-8.
Schulam PG, et al. Platelet-activating Factor Induces Phospholipid Turnover, Calcium Flux, Arachidonic Acid Liberation, Eicosanoid Generation, and Oncogene Expression in a Human B Cell Line. J Immunol. 1991 Mar 1;146(5):1642-8. PubMed PMID: 1847170.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Platelet-activating factor induces phospholipid turnover, calcium flux, arachidonic acid liberation, eicosanoid generation, and oncogene expression in a human B cell line. AU - Schulam,P G, AU - Kuruvilla,A, AU - Putcha,G, AU - Mangus,L, AU - Franklin-Johnson,J, AU - Shearer,W T, PY - 1991/3/1/pubmed PY - 1991/3/1/medline PY - 1991/3/1/entrez SP - 1642 EP - 8 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 146 IS - 5 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/1847170/Platelet_activating_factor_induces_phospholipid_turnover_calcium_flux_arachidonic_acid_liberation_eicosanoid_generation_and_oncogene_expression_in_a_human_B_cell_line_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=1847170 DB - PRIME DP - Unbound Medicine ER -