Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0808492 on January 21, 2009

Published online before print January 21, 2009
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(Journal of Leukocyte Biology. 2009;85:656-663.)
© 2009 by Society for Leukocyte Biology

Crucial implication of protein kinase C (PKC)-{delta}, PKC-{zeta}, ERK-1/2, and p38 MAPK in migration of human asthmatic eosinophils

Anick Langlois*, Francois Chouinard*, Nicolas Flamand*, Claudine Ferland*, Marek Rola-Pleszczynski{dagger} and Michel Laviolette*,1

* Unité de Recherche en Pneumologie, Centre de Recherche de l’Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l’Université Laval, Québec City, Quebec, Canada; and
{dagger} Immunology Division, Department of Pediatrics, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada

1 Correspondence: Hôpital Laval, 2725 Chemin Sainte-Foy, Québec City, Quebec, Canada, G1V 4G5. E-mail: michel.laviolette{at}med.ulaval.ca

Asthma is associated with an eosinophil infiltration into the bronchial mucosa. 5-Oxo-6,8,11,14(E,Z,Z,Z)-eicosatetraenoic acid (5-oxo-ETE), a potent eosinophil chemotactic factor, activates cell motility, adherence, and proteolysis, notably, by promoting CD11b expression, matrix metalloproteinase (MMP)-9 secretion, and plasmin generation. We investigated the intracellular signaling pathways implicated in these various steps by using different, selective inhibitors. Human eosinophil migration through a reconstituted basement membrane in response to 5-oxo-ETE was greatly inhibited (≥72%) by the protein kinase C (PKC)-{delta}, PKC-{zeta}, ERK-1/2, and p38 inhibitors. Our findings indicate that PKC-{delta} mediates cell motility, CD11b expression, and MMP-9 granule release. PKC-{zeta} is also largely involved in eosinophil migration, although its specific targets remain undefined. ERK-1/2 and p38 modulate CD11b expression; ERK-1/2 is also involved in long-term MMP-9 secretion and p38 in the plasmin activation system. We demonstrated the crucial implication of PKC-{delta}, PKC-{zeta}, ERK-1/2, and p38 in human blood eosinophil migration through extracellular matrix components. Targeting specific pathways may have therapeutic potential for the treatment of allergic airway inflammation.

Key Words: matrix metalloproteinase • urokinase plasminogen activator • plasmin • 5-oxo-6 • 8 • 11 • 14(E,Z,Z,Z)-eicosatetraenoic acid • mitogen-activated protein kinase