Modulation by dexamethasone of phospholipase a2 activities in
endotoxemic guinea-pigs.
Decastro, C[acute]elia M. M. B., Michel F. Bureau, Marie-Anne Nahori,
Claude H. Dumarey, B. Boris Vargaftig, Maria Bachelet.
Unit[acute]e de Pharmacologie Cellulaire, Unit[acute]e
Associ[acute]ee Institut Pasteur-INSERM 285, 25 rue du Dr Roux,
75724, Paris C[acute]edex 15, France, Tel: (33-1) 45 68 86 89, Fax:
(33-1) 45 68 87 03
APStracts 2:0224A, 1995.
One hour following LPS administration (i.v.) to guinea-pigs, alveolar
macrophages are primed for an ex vivo increased secretion of
arachidonic acid metabolites from the cyclooxygenase and the
lipoxygenase pathways, upon challenge by a second stimulus. At the
same time, maximal levels of TNF[alpha] are observed in the
circulation and in the bronchoalveolar lavage fluid. An extracellular
form of phospholipase A2, corresponding probably to the low molecular
weight type II enzyme, known to accumulate in inflammatory exudates,
appears later in the serum of guinea-pigs, to reach maximal levels 6
h following the LPS injection. Unlike the intracellular enzyme,
extracellular phospholipase A2 is not increased by LPS in alveolar
macrophages or in bronchoalveolar lavage fluids. After 24 h, at the
time when neither TNF[alpha] nor extracellular phospholipase A2 are
present and priming of macrophages is over, maximal neutrophil
infiltration is observed in the alveolar space of LPS-treated guinea
-pigs. Dexamethasone administered repeatedly during three days (s.c.)
before the LPS challenge, prevented both early events as the
macrophage priming and the TNF[alpha] appearence and later events as
extracellular phospholipase A2 release and neutrophil recruitment.
Received 7 December 1994; accepted in final form 12 May 1995.
APS Manuscript Number A1245-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.