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Angiostatin Inhibits Neutrophil Migration and Activation
Author(s) -
Aulakh Gurpreet Kaur,
Singh Baljit
Publication year - 2011
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.25.1_supplement.116.5
Subject(s) - microbiology and biotechnology , chemistry , p38 mitogen activated protein kinases , intravital microscopy , in vitro , chemotaxis , apoptosis , in vivo , phosphorylation , biology , mapk/erk pathway , biochemistry , receptor
Dysregulated recruitment of activated neutrophils contributes to tissue damage, morbidity and mortality. Here, we studied the role of angiostatin (ANG), an anti‐angiogenic molecule, in neutrophil recruitment and activation in vivo and in vitro . First, we showed lipid raft mediated surface and cytosolic localization of FITC‐conjugated ANG in fMLP‐activated but not resting mouse and human neutrophils. ANG co‐localised with neutrophil α‐tubulin, angiomotin and β 3 integrin in response to fMLP. ANG inhibited the signal for reduced mitotracker dye, an index of neutrophil activation in suspended as well as adhered neutrophils in response to fMLP and LPS. ANG also inhibited the signal for phosphorylated forms of hsp‐27, p38 and p44/42 MAPK that regulate neutrophil activation. Finally, ANG blocked formation of reactive oxygen species while activating caspase‐3 and inducing apoptosis in LPS‐activated neutrophils. In‐vitro confocal microscopy on mouse as well as human neutrophils revealed that ANG abolished fMLP‐induced polarisation of actin‐rich leading edge. Intravital microscopy showed that ANG reduced leukocyte adhesion and emigration (p<0.05) and simultaneously increased rolling flux (p<0.05) in post‐capillary venules in TNFα‐treated cremaster muscles. We conclude that ANG is a novel inhibitor of neutrophil migration and activation. (Funding NSERC Discovery Grant) Grant Funding Source : NSERC Discovery Grant