Visit our Expo - Redox and Inflammation signaling 2012

Session III : Protein kinase cascades as therapeutic targets Poster III, 11
Anaphylactic shock critically depends on PI3K and eNOS-derived NO
Anje Cauwels1, Ben Janssen2 and Peter Brouckaert1
1Department for Molecular Biomedical Research, Ghent University and VIB,
Technologiepark 927, B-9052 Ghent, Belgium; 2Department of Pharmacology and
Toxicology, University of Maastricht, Maastricht 6200 MD, The Netherlands
Anaphylaxis is an acute, severe and life-threatening systemic allergic reaction that occurs
after the reexposure to a specific antigen. Allergens include insect stings, medications,
antibiotics, anesthetics, contrast materials, certain foods, latex exposure or even exercise. A
serious anaphylactic reaction is associated with severe hypotension and requires immediate
parenteral treatment with epinephrine and aggressive volume resuscitation. However,
anaphylactic cardiovascular collapse can be resistant to epinephrine and intravenous fluids.
Platelet activating factor (PAF) is implicated in the cardiovascular dysfunctions occurring in
various shock syndromes, including anaphylaxis. It is generally accepted that the excessive
production of the vasodilator nitric oxide (NO) causes inflammatory hypotension and shock.
NO may be produced by the constitutive NO synthases eNOS (NOS3) or nNOS (NOS1), or
by the transcriptionally regulated inducible iNOS (NOS2). At this time, iNOS is regarded to
be the major producer of shock-inducing NO. Nevertheless, the contribution of NO to PAFinduced
or anaphylactic shock is still ambiguous. We studied PAF and anaphylactic shock in
conscious mice. Surprisingly, hyperacute PAF or anaphylactic shock and mortality entirely
depended on NO, produced not by the inducible iNOS but by the constitutive eNOS, rapidly
activated via the (alternative) phosphatidylinositol-3-kinase (PI3K) pathway. In contrast to the
unsubstantiated axioma that only excessive iNOS-derived NO underlies cardiovascular
collapse in shock, our data support the surprising concept that eNOS-derived NO is the
principal vasodilator in PAF-induced or anaphylactic shock and define eNOS and/or PI3K as
new possible targets for treating anaphylaxis.
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