Oscillatory pericellular proteolysis and oxidant deposition during neutrophil locomotion

Biophysical Journal
A L KindzelskiiH R Petty

Abstract

To better understand the mechanism of leukocyte migration in complex environments, model extracellular matrices were prepared using gelatin, Hanks' solution, Bodipy-BSA (fluorescent upon proteolysis), and dihydrotetramethylrosamine or hydroethidine (fluorescent upon oxidation). Using quantitative microfluorometry, neutrophil-mediated extracellular pulses of reactive oxygen metabolites (ROMs) and pericellular proteolysis were periodically observed showing that these functions occur as quantal bursts. However, chronic granulomatous disease neutrophils, which do not produce ROMs, did not display ROM deposition. Matrices show an alternating pattern of green (proteolytic) and red (oxidative) fluorescence, indicating these functions are out of phase. Electric fields phase-matched with metabolic oscillations, which increase the amplitude of intracellular NAD(P)H oscillations, increase ROM deposition and pericellular proteolysis; this further supports the link between intracellular chemical oscillators and extracellular functions. This phase relationship may allow ROMs to inactivate protease inhibitors, followed by protease activation.

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Citations

Jun 5, 2003·Chaos·John M. EmlenJohn H. Graham
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·H R Petty, A L Kindzelskii
Jun 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Andrei L Kindzelskii, Howard R Petty
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·E Albrecht, H R Petty
May 2, 2006·The Journal of Alternative and Complementary Medicine : Research on Paradigm, Practice, and Policy·Vladimir L Voeikov
Dec 19, 2002·The Journal of Clinical Investigation·Andrei L KindzelskiiHoward R Petty
Sep 5, 2008·PloS One·Ildefonso M De La FuenteAntonio Vera-López
Nov 6, 2009·PloS One·Ildefonso M De la FuenteJuan Veguillas
Mar 9, 2010·PloS One·Ildefonso M De la FuenteAntonio Vera-López
Oct 20, 2010·International Journal of Molecular Sciences·Ildefonso Martínez de la Fuente
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