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Crucial implication of protein kinase C (PKC)‐δ, PKC‐ζ, ERK‐1/2, and p38 MAPK in migration of human asthmatic eosinophils
Author(s) -
Langlois Anick,
Chouinard Francois,
Flamand Nicolas,
Ferland Claudine,
RolaPleszczynski Marek,
Laviolette Michel
Publication year - 2009
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0808492
Subject(s) - protein kinase c , p38 mitogen activated protein kinases , biology , mapk/erk pathway , microbiology and biotechnology , kinase , mitogen activated protein kinase , protein kinase a , immunology
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)‐δ, PKC‐ζ, ERK‐1/2, and p38 inhibitors. Our findings indicate that PKC‐δ mediates cell motility, CD11b expression, and MMP‐9 granule release. PKC‐ζ 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‐δ, PKC‐ζ, 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.