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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hallett, Maurice B. Dewitt, Sharon |
| Description | Author Affiliation: Dewitt S ( Neutrophil Signalling Group, University Department of Surgery, University of Wales College of Medicine, Cardiff CF14 4XN, United Kingdom.) |
| Abstract | 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 $Ca^{2+}$ imaging, the temporal relationship between changes in cytosolic free $Ca^{2+}$ concentration and phagocytosis were correlated. Here we show that whereas small, localized $Ca^{2+}$ 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 $Ca^{2+}$ which resulted from $Ca^{2+}$ influx. This latter rise in cytosolic free $Ca^{2+}$ concentration also liberated a fraction of β2 integrin receptors which were initially immobile on the neutrophil surface, as demonstrable by both fluorescence recovery after laser bleaching and by visualization of localized β2 integrin labelling. Inhibitors of calpain activation prevented both the $Ca^{2+}-induced$ liberation of β2 integrin and the rapid stage of phagocytosis, despite the persistence of the global $Ca^{2+}$ signal. Therefore, we propose that $Ca^{2+}$ activation of calpain causes β2 integrin liberation, and that this signal plays a key role in the acceleration of β2 integrin–mediated phagocytosis. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 1 |
| Volume Number | 159 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2002-10-14 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antigens, CD18 Metabolism Calcium Calpain Neutrophils Physiology Phagocytosis Antigens, CD11b Calcium Signaling Antagonists & Inhibitors Cell Size Chelating Agents Complement C3b Cysteine Proteinase Inhibitors Enzyme Activation Fluorescence Recovery After Photobleaching Fluorescent Dyes Fura-2 Cytology Zymosan Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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