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Blood, 1 December 2000, Vol. 96, No. 12, pp. 3809-3815
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Secreted phospholipase A2 induces vascular
endothelial cell migration
Maria Teresa Rizzo,
Elisabeth Nguyen,
Marlene Aldo-Benson, and
Gerard Lambeau
From the Signal Transduction Laboratory, Methodist
Research Institute and Arthritis Care Center, Clarian Health,
Indianapolis, and the Institut de Pharmacologie Moleculaire et
Cellulaire, CNRS-UPR, Sophia Antipolis, Valbonne, France.
Secreted phospholipase A2 (sPLA2) regulates
a variety of cellular functions. The present investigation was
undertaken to elucidate the potential role of sPLA2 in
endothelial cell (EC) migration. Bovine aortic endothelial cells
(BAECs) exposed to sPLA2 placed in the lower compartment of
a modified Boyden chamber displayed increased migration compared to
cells exposed to vehicle. The effect of sPLA2 on EC
migration was time and dose dependent. Migration of BAECs was observed
at 30 minutes, increased over 1 to 2 hours, and declined thereafter. At
2 hours of stimulation, sPLA2 (0.01-2 µmol/L) induced
1.2- to 3-fold increased cell migration compared with media alone.
Among the different sPLA2s tested, bee venom, Naja naja,
and porcine and human pancreatic PLA2s all evoked a migratory response in ECs. Moreover, human synovial fluid, obtained from patients with arthritis and containing sPLA2 activity,
induced EC migration. Migration of ECs was significantly reduced after exposure to a catalytic site mutant of pancreatic sPLA2
with decreased lipolytic activity as compared to wild-type
sPLA2. Similarly, pretreatment of human synovial fluid with
p-bromophenacyl bromide, an irreversible inhibitor of
sPLA2, markedly decreased the ability of human synovial
fluid to stimulate EC migration. Moreover, migration of ECs was
stimulated on exposure to hydrolytic products of sPLA2 activity including arachidonic acid, lysophosphatidic acid, and lysophosphatidylcholine. These findings suggest that sPLA2
plays a physiologic role in induction of EC migration. Moreover, the effects of sPLA2 on EC migration are mediated, at least in
part, by its catalytic activity.
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