Hemodynamic Stress Enhances Neutrophil Responsiveness to Chemotactic Stimuli

Abstract

Circulating neutrophils are exposed to widely varying levels of hemodynamic stress induced by blood flow conditions. This study examined the effect of hemodynamic stress on the functional responsiveness of neutrophils obtained from healthy humans to chemotactic stimuli. To expose neutrophils to hemodynamic stress in vitro, isolated neutrophils were agitated under artificial flow conditions induced by a rotary tube apparatus. Although such hemodynamic stress produced no spontaneous or random migration of neutrophils, it enhanced neutrophil migration in response to the chemotactic peptide f-methionyl-leucyl-phenylalanine (FMLP) by as much as 200%. Hemodynamic stress also enhanced polarization in response to FMLP, producing a change in shape characteristic of migration. Polarization was reversible when neutrophils were transferred to quiescent conditions after being exposed, to hemodynamic stress. Hemodynamic stress also enhanced O−2 production and granular β-glucuronidase release in response to FMLP and enhanced polarization and O−2 production in response to phorbol myristate acetate (PMA), a direct activator of protein kinase C. Extracellular Ca2+ was not required for the enhancement of chemotactic responsiveness by hemodynamic stress, and the stress produced no detectable change in intracellular Ca2+, intracellular cyclic AMP, or activated protein kinase C levels in neutrophils. The results show that hemodynamic stress enhances the functional responsiveness of neutrophils to chemotactic stimuli and provide insights into interpretation of in vitro data usually obtained from quiescent conditions.