ARACHIDONIC-ACID TURNOVER IN RESPONSE TO LIPOPOLYSACCHARIDE AND OPSONIZED ZYMOSAN IN HUMAN MONOCYTE-DERIVED MACROPHAGES

被引:33
作者
LESLIE, CC
DETTY, DM
机构
[1] NATL JEWISH CTR IMMUNOL & RESP MED, DEPT PEDIAT, 1400 JACKSON ST, DENVER, CO 80206 USA
[2] UNIV COLORADO, HLTH SCI CTR, DEPT PATHOL, DENVER, CO 80262 USA
关键词
D O I
10.1042/bj2360251
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
Macrophages are an important source of the lipid mediators, arachidonic acid metabolites and platelet-activating factor (PAF), produced during inflammation. Studies were undertaken to identify the phospholipid substrates that can serve as a source of arachidonic acid in human monocyte-derived macrophages exposed to the inflammatory stimuli bacterial lipopolysaccharide (LPS) and opsonized zymosan (OpZ). Since PAF is derived from 1-alkyl-2-acyl-glycerophosphocholine, it was of interest to determine if this phospholipid precursor could also serve as a source of arachidonic acid. The day-5 macrophages incorporated 38% of the available [3H]arachidonic acid into lipid by 4 h, 54% of which was in phospholipid [phosphatidylcholine (PC) > phosphatidylethanolamine (PE) > phosphatidylinositol (PI)]. The proportion of label incorporated into ether-linked PC and PE increased with time. After prelabelling with [3H]arachidonic acid, the effect of stimuli on the redistribution of label within phospholipids was followed. Without stimulus there was a loss of label from PC, PI and phosphatidic acid by 3 h, but an increase of label in PE. The [3H]arachidonic acid that was lost from PC in the absence of stimulus was derived solely from the 1-acyl-linked species of PC, whereas an increase in label occurred in the 1-alkyl-linked species of PC. By contrast, LPS stimulation resulted in a preferential, dose-dependent loss of label from PC and PI, which was maximal between 1 and 3 h after adding the LPS. In addition, LPS induced a 35% decrease in the molar quantity of PI in the macrophages but had no effect on the quantity of PC, PE or phosphatidylserine. Stimulation with OpZ also resulted in a loss of label, mainly from PC and PI. Of the total label lost from PC in response to LPS or OpZ, approx. 50% was derived from the 1-alkyl-linked species. The results suggest that phospholipase C- and phospholipase A2-mediated mechanisms for arachidonic acid release are activated in human macrophages exposed to the inflammatory stimuli LPS and OpZ. In addition, 1-alkyl-linked PC can serve as a source of arachidonic acid and as a precursor for PAF production in the stimulated macrophages.
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页码:251 / 259
页数:9
相关论文
共 40 条
[1]   RELEASE OF ARACHIDONIC-ACID FROM 1-ALKYL-2-ACYL-SN-GLYCERO-3-PHOSPHOCHOLINE, A PRECURSOR OF PLATELET-ACTIVATING FACTOR, IN RAT ALVEOLAR MACROPHAGES [J].
ALBERT, DH ;
SNYDER, F .
BIOCHIMICA ET BIOPHYSICA ACTA, 1984, 796 (01) :92-101
[2]  
ALBERT DH, 1983, J BIOL CHEM, V258, P97
[3]  
Benveniste J., 1983, ETHER LIPIDS BIOCH B, P355
[4]   INOSITOL TRISPHOSPHATE AND DIACYLGLYCEROL AS 2ND MESSENGERS [J].
BERRIDGE, MJ .
BIOCHEMICAL JOURNAL, 1984, 220 (02) :345-360
[5]  
BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911
[6]   REGULATION OF PROSTAGLANDIN SYNTHESIS AND OF SELECTIVE RELEASE OF LYSOSOMAL HYDROLASES BY MOUSE PERITONEAL MACROPHAGES [J].
BONNEY, RJ ;
WIGHTMAN, PD ;
DAVIES, P ;
SADOWSKI, SJ ;
KUEHL, FA ;
HUMES, JL .
BIOCHEMICAL JOURNAL, 1978, 176 (02) :433-442
[7]  
CHAM BE, 1976, J LIPID RES, V17, P176
[8]   ARACHIDONIC-ACID METABOLISM AND MACROPHAGE ACTIVATION [J].
CHENSUE, SW ;
KUNKEL, SL .
CLINICS IN LABORATORY MEDICINE, 1983, 3 (04) :677-694
[9]  
CHILTON FH, 1983, J BIOL CHEM, V258, P7268
[10]  
CHILTON FH, 1984, J BIOL CHEM, V259, P2014