Visit our Expo - Redox and Inflammation signaling 2012

VIII. Inflammation specific signaling Poster VIII, 21
Insulin primes human neutrophils for CCL3-induced migration: crucial role for JNK.
Fabrizio Montecucco, Giordano Bianchi, Luciano Ottonello, Maria Bertolotto, Giorgio
L. Viviani and Franco Dallegri.
Clinic of Internal Medicine I, Department of Internal Medicine, University of Genoa
Medical School, I-16132 Genoa, Italy. E-mail: fabriziomontecucco@tiscali.it
Recent studies showing that neutrophil infiltration in unstable atherosclerotic lesions is
associated with plaque rupture have suggested a pathogenetic role for neutrophils in
atherosclerosis. Nevertheless, the mechanisms regulating the recruitment of neutrophils at
sites of atherosclerotic lesions are still unknown. In this regard, it has been recently shown
that insulin is involved in actin reorganization of neutrophil locomotory response. Thus, we
studied the effects of > 50 microU/ml insulin, i.e. concentrations occurring in
hyperinsulinemic conditions characterized by an increased atherosclerotic risk, on neutrophil
migration to CCL3, a chemokine produced in atherosclerotic plaques and considered to be
incapable of attracting human neutrophils. Neutrophils from healthy volunteers became
capable of migrating to CCL3 after a short (15 min) exposure to 300 microU/ml insulin.
Accordingly, although no [Ca2+]i mobilization was observed in response to CCL3 or insulin,
the combination of insulin and CCL3 stimulation results in a well detectable [Ca2+]i spike.
Furthermore, the exposure of neutrophils to serum from hyperinsulinemic and euglycaemic
adult patients with metabolic syndrome (as defined by ATP III and WHO criteria), induced
neutrophil responsiveness to CCL3. A strict correlation (p: