ALTERATION OF LIPID-COMPOSITION MODULATES FC-EPSILON-RI SIGNALING IN RBL-2H3 CELLS

被引：22

作者：

CHANG, EY ^{[1
]}

ZHENG, Y ^{[1
]}

HOLOWKA, D ^{[1
]}

BAIRD, B ^{[1
]}

机构：

[1] CORNELL UNIV,DEPT CHEM,ITHACA,NY 14853

来源：

BIOCHEMISTRY | 1995年 / 34卷 / 13期

关键词：

D O I：

10.1021/bi00013a029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 A(2) 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 a similar to 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 (greater than or equal to 16 h) with 100 nM PMA or short-term treatment(10 min) with 5 mu M 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. Our results support the hypothesis that membrane structure plays an important role in regulating the activation of downstream signaling pathways by activated receptor complexes.

引用

页码：4376 / 4384

页数：9

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