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Oxidized Phospholipids Inhibit Migration of Mononuclear Phagocytes
Author(s) -
Ostankovitch Marina Irene,
Iwanicki Marcin,
Hamandi Hassan,
Leitinger Norbert
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a17-a
Subject(s) - focal adhesion , inflammation , cell migration , microbiology and biotechnology , chemistry , phosphorylcholine , phosphorylation , tyrosine phosphorylation , peripheral blood mononuclear cell , cancer research , immunology , biology , in vitro , biochemistry
Mononuclear phagocytes (MP) accumulate in atherosclerotic plaques, where they contribute to disease progression, promoting prolonged inflammation. This study investigated whether oxidized phospholipids (OxPL), produced in atherosclerotic lesions, play a role in inhibiting the migration of MP. Using phase‐contrast time‐lapse microscopy, OxPL 1‐palmitoyl‐2‐(5‐oxovaleroyl)‐ sn ‐glycero‐3‐phosphorylcholine (POVPC) inhibits the migration of bone‐marrow‐derived macrophages. In order to study the effect of OxPL on migration of MP in vivo , we used a mouse model where tape stripping induced a disruption of the epidermis that led to inflammation and migration of dermal MP to draining lymph nodes. Epicutaneous application of POVPC inhibited migration of dermal MP. In order to uncover the mechanism by which POVPC inhibited migration of MP, we assessed the impact of POVPC on the activation of Focal Adhesion Kinase (FAK) and Proline‐rich tyrosine kinase‐2 (PYK2), which has been implicated in controlling MP migration. We show that POVPC decreased the phosphorylation status of FAK and PYK2, in MP. Our data suggest that at inflammatory sites, POVPC is involved in the regulation of migratory events in MP by disrupting major migratory signaling pathways through inhibition of FAK and PYK2. We propose that OxPL contribute to the formation of atherosclerotic plaques by preventing migration of MP out of the lesions.