Alteration of lipid composition modulates Fc epsilon RI signaling in RBL-2H3 cells.
We have used sonicated liposomes of phosphatidylcholine (PC), sphingomyelin (SM), or a mixture of cholesterol (chol) and PC to investigate the role of cellular lipid composition in Fc epsilon RI-mediated stimulation of RBL-2H3 cells. Overnight treatment with either PC or SM liposomes causes a substantial enhancement of antigen-stimulated degranulation and phospholipase A2 activity, whereas treatment with a PC/chol mixture results in partial inhibition of the antigen-stimulated response. The most consistent change in the cellular lipid composition that results from the PC and SM liposome treatments is an approximate 40% decrease in the chol/phospholipid (PL) ratio. The lipid treatments do not alter degranulation stimulated by AlF4- or by Ca2+ ionophore in the presence or absence of PMA, suggesting that lipid alteration affects a receptor-specific signaling process. The lipid treatments do not appear to alter antigen-stimulated tyrosine phosphorylation or Ca2+ mobilization. Possible involvement of protein kinase C (PKC) activation in the signal-enhancing effect of the PL treatments was investigated by using calphostin C and phorbol-12-myristol-13-acetate (PMA) to inhibit PKC activity and degranulation in RBL-2H3 cells. Both SM and PC treatment restore the antigen-mediated degranulation response that is inhibited by long-term treatment (> or = 16 h) with 100 nM PMA or short-term treatment (10 min) with 5 microM calphostin C. The results indicate that a decreased chol/PL ratio facilitates or enhances the receptor-mediated activation of a PKC-like pathway that plays an important role in Fc epsilon RI-stimulated degranulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Chang
E Y
EY
Department of Chemistry, Cornell University, Ithaca, New York 14853, USA.
Zheng
Y
Y
Holowka
D
D
Baird
B
B
D000941:Antigens / Q000276:immunology; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D002784:Cholesterol / Q000032:analysis / Q000494:pharmacology; D004140:Dinitrophenols / Q000276:immunology; D008081:Liposomes; D008563:Membrane Lipids / Q000032:analysis* / Q000494:pharmacology / Q000502:physiology*; D010713:Phosphatidylcholines / Q000032:analysis / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000032:analysis; D017455:Receptors, IgE / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*; D013010:Sonication; D013109:Sphingomyelins / Q000032:analysis / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium
D000941:Antigens; D004140:Dinitrophenols; D008081:Liposomes; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D017455:Receptors, IgE; D013109:Sphingomyelins; C034638:dinitrophenyl-bovine serum albumin; D014316:Tritium; D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; D012701:Serotonin; D000001:Calcimycin; D002784:Cholesterol; D010741:Phospholipases A; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate