The role of calcium and phosphorylation of cytosolic phospholipase A2 in regulating arachidonic acid release in macrophages

被引:177
作者
Qiu, ZH
Gijón, MA
de Carvalho, MS
Spencer, DM
Leslie, CC
机构
[1] Natl Jewish Med & Res Ctr, Dept Pediat, Div Basic Sci, Denver, CO 80206 USA
[2] Univ Colorado, Sch Med, Dept Pathol, Denver, CO 80262 USA
关键词
D O I
10.1074/jbc.273.14.8203
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
Arachidonic acid release is induced in macrophages with diverse agonists including calcium ionophores, phorbol myristate acetate (PMA), okadaic acid, and the phagocytic particle, zymosan, and correlates with activation of cytosolic phospholipase A(2) (cPLA(2)). The role of calcium and phosphorylation of cPLA(2) in regulating arachidonic acid release was investigated, Zymosan induced a rapid and transient increase in [Ca2+](i). This in itself is not sufficient to induce arachidonic acid release since ATP and platelet activating factor (PAF), agonists that induce transient calcium mobilization in macrophages, induced little arachidonic acid release, Unlike zymosan, which is a strong activator of mitogen-activated protein kinase (MAPK), ATP and PAF were weak MAPK activators and induced only a partial and transient increase in cPLA(2) phosphorylation (gel shift). However, ATP or PAF together with colony stimulating factor-1 (CSF-1) synergistically stimulated arachidonic acid release, CSF-1 is a strong MAPK activator that induces a rapid and complete cPLA(2) gel shift but not calcium mobilization or arachidonic acid release, Arachidonic acid release was more rapid in response to CSF-1 plus ATP or PAF than zymosan and correlated with the time course of the cPLA(2) gel shift. Although low concentrations of ionomycin induced a lower magnitude of calcium mobilization than ATP, the response was more sustained resulting in arachidonic acid release, A23187 and ionomycin induced weak MAPK activation, and a partial and transient cPLA(2) gel shift. The MAPK kinase inhibitor, PD 98059 suppressed A23187-induced MAPK activation and cPLA(2) gel shift but had little effect on arachidonic acid release. These results indicate that in macrophages a transient increase in [Ca2+](i) and sustained phosphorylation of cPLA(2) can act together to promote arachidonic acid release but neither alone is sufficient. A sustained increase in calcium is sufficient for inducing arachidonic acid release. However, PMA and okadaic acid induce arachidonic acid release without increasing [Ca2+](i), although resting levels of calcium are required, suggesting alternative mechanisms of regulation.
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页码:8203 / 8211
页数:9
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共 32 条
[1]  
ALONSOTORRE SR, 1993, J BIOL CHEM, V268, P18640
[2]   ROLE OF CYTOSOLIC PHOSPHOLIPASE A(2) IN ARACHIDONIC-ACID RELEASE OF RAT-LIVER MACROPHAGES - REGULATION BY CA2+ AND PHOSPHORYLATION [J].
AMBS, P ;
BACCARINI, M ;
FITZKE, E ;
DIETER, P .
BIOCHEMICAL JOURNAL, 1995, 311 :189-195
[3]   PATHWAYS FOR ARACHIDONIC-ACID MOBILIZATION IN ZYMOSAN-STIMULATED MOUSE PERITONEAL-MACROPHAGES [J].
BALSINDE, J ;
FERNANDEZ, B ;
SOLISHERRUZO, JA ;
DIEZ, E .
BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1136 (01) :75-82
[4]  
CHANNON JY, 1990, J BIOL CHEM, V265, P5409
[5]   MECHANISMS OF PLATELET-DERIVED GROWTH FACTOR-INDUCED ARACHIDONIC-ACID RELEASE IN SWISS-3T3 FIBROBLASTS - THE ROLE OF A LOCALIZED INCREASE IN FREE CA2+ CONCENTRATION BENEATH THE PLASMA-MEMBRANE AND THE ACTIVATION OF PROTEIN-KINASE-C [J].
CHOW, SC ;
POWIS, G .
BIOCHIMICA ET BIOPHYSICA ACTA, 1993, 1179 (01) :81-88
[6]   A NOVEL ARACHIDONIC ACID-SELECTIVE CYTOSOLIC PLA2 CONTAINS A CA2+-DEPENDENT TRANSLOCATION DOMAIN WITH HOMOLOGY TO PKC AND GAP [J].
CLARK, JD ;
LIN, LL ;
KRIZ, RW ;
RAMESHA, CS ;
SULTZMAN, LA ;
LIN, AY ;
MILONA, N ;
KNOPF, JL .
CELL, 1991, 65 (06) :1043-1051
[7]   CYTOSOLIC PHOSPHOLIPASE A(2) [J].
CLARK, JD ;
SCHIEVELLA, AR ;
NALEFSKI, EA ;
LIN, LL .
JOURNAL OF LIPID MEDIATORS AND CELL SIGNALLING, 1995, 12 (2-3) :83-117
[8]   Identification of phosphorylation sites of human 85-kDa cytosolic phospholipase A(2) expressed in insect cells and present in human monocytes [J].
deCarvalho, MGS ;
McCormack, AL ;
Olson, E ;
Ghomashchi, F ;
Gelb, MH ;
Yates, JR ;
Leslie, CC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (12) :6987-6997
[9]   THE 85-KDA, ARACHIDONIC ACID-SPECIFIC PHOSPHOLIPASE-A(2) IS EXPRESSED AS AN ACTIVATED PHOSPHOPROTEIN IN SF9 CELLS [J].
DECARVALHO, MS ;
MCCORMACK, FX ;
LESLIE, CC .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1993, 306 (02) :534-540
[10]   PROTEIN KINASE-C ACTIVATION OF PHYSIOLOGICAL PROCESSES IN HUMAN-NEUTROPHILS AT VANISHINGLY SMALL CYTOSOLIC CA-2+ LEVELS [J].
DIVIRGILIO, F ;
LEW, DP ;
POZZAN, T .
NATURE, 1984, 310 (5979) :691-693