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Neutrophil Signalling Group, University Department of Surgery, University of Wales College of Medicine, Cardiff CF14 4XN, United Kingdom

Address correspondence to Dr. Maurice Hallet, Neutrophil Signalling Group, University Dept. of Surgery, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, U.K. Tel.: 44-29-2074-2748. Fax: 44-29-2076-1623. E-mail: hallettmb{at}cf.ac.uk

Phagocytosis of microbes coated with opsonins such as the complement component C3bi is the key activity of neutrophils. However, the mechanism by which opsonins enhance the rate of phagocytosis by these cells is unknown and has been difficult to study, partly because of the problem of observing and quantifying the events associated with phagocytosis. In this study, C3bi-opsonized particles were presented to neutrophils with a micromanipulator, so that the events of binding, pseudopod cup formation, engulfment, and completion of phagocytosis were clearly defined and distinguished from those involved with chemotaxis. Using this approach in combination with simultaneous phase contrast and Ca²⁺ imaging, the temporal relationship between changes in cytosolic free Ca²⁺ concentration and phagocytosis were correlated. Here we show that whereas small, localized Ca²⁺ changes occur at the site of particle attachment and cup formation as a result of store release, rapid engulfment of the particle required a global change in cytosolic free Ca²⁺ which resulted from Ca²⁺ influx. This latter rise in cytosolic free Ca²⁺ concentration also liberated a fraction of ß2 integrin receptors which were initially immobile on the neutrophil surface, as demonstrable by both fluorescence recovery after laser bleaching and by visualization of localized ß2 integrin labelling. Inhibitors of calpain activation prevented both the Ca²⁺-induced liberation of ß2 integrin and the rapid stage of phagocytosis, despite the persistence of the global Ca²⁺ signal. Therefore, we propose that Ca²⁺ activation of calpain causes ß2 integrin liberation, and that this signal plays a key role in the acceleration of ß2 integrin–mediated phagocytosis.

Key Words: neutrophil; phagocytosis; Ca²⁺ signalling; integrin; C3bi

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