Increased cyclooxygenase-2 and 5-lipoxygenase activating protein expression in peritoneal macrophages during ovalbumin immunization of mice and cytosolic phospholipase A(2) activation after antigen challenge.
The present study investigates phenotypic and functional differentiation of peritoneal macrophages during ovalbumin-induced subcutaneous immunization of mice. For the first time we show that, in mouse peritoneal macrophages, ovalbumin immunization induces an increase in cyclooxygenase-2 (COX-2) and 5-lipoxygenase activating protein (FLAP) expression whereas it inhibits cytosolic phospholipase A(2) (cPLA2) expression. The study of arachidonic acid (AA) metabolism in peritoneal macrophages from control (cPM) and ovalbumin-immunized (iPM) mice shows that the reduced cPLA2 expression is correlated to a reduced basal AA metabolism, but is not a limiting factor for the opsonized zymosan-, PMA-, or A23187-triggered AA metabolism. We also show that in vitro ovalbumin challenge induces, only in iPM, cPLA2 activation through phosphorylation of serine residues, via a mechanism involving MAP kinases, and through increased intracellular calcium concentrations, leading to eicosanoid production. In parallel, we report that, in peritoneal macrophages, ovalbumin immunization induces the expression of CD23, the low affinity receptor for IgEs known for its involvement in allergic diseases. Thus, the modified expression of the enzymes involved in AA metabolism and the difference of response of cPM and iPM toward the antigen are important elements to understand the underlying mechanisms of ovalbumin-induced allergic responses.
Escoubet
L
L
Université Paul Sabatier UPRES EA 2405, Macrophages Inflammatory Mediators and Cellular Interactions, INSERM IFR31, CHU Rangueil, 1, Avenue Jean Poulhès, 31403 Toulouse Cedex 4, France.
Rey
A
A
Wong
A
A
Bernad
J
J
Lepert
J C
JC
Orfila
C
C
Pipy
B
B
D058927:5-Lipoxygenase-Activating Proteins; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis*; D051546:Cyclooxygenase 2; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D007114:Immunization; D007279:Injections, Subcutaneous; D007527:Isoenzymes / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D010741:Phospholipases A / Q000378:metabolism*; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D017455:Receptors, IgE / Q000096:biosynthesis; D014316:Tritium
D058927:5-Lipoxygenase-Activating Proteins; C548593:Alox5ap protein, mouse; D002352:Carrier Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D017455:Receptors, IgE; D014316:Tritium; D016718:Arachidonic Acid; D010047:Ovalbumin; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D002118:Calcium