Research ArticleChemotaxis

Extension of chemotactic pseudopods by nonadherent human neutrophils does not require or cause calcium bursts

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Science Signaling  13 Mar 2018:
Vol. 11, Issue 521, eaal4289
DOI: 10.1126/scisignal.aal4289

Calcium bursts in neutrophil chemotaxis

Immune cells migrate toward pathogens using chemotactic cues that are either pathogen-derived or generated by the host, such as components of the complement system. During chemotaxis and phagocytosis, the cells coordinate receptor-based signaling with the mechanical processes that underlie adhesion, cell deformation, and migration. To investigate the physiological role of intracellular calcium (Ca2+) bursts in this complex behavior, Francis and Heinrich presented nonadherent human neutrophils with various targets that induced complement-mediated chemotaxis. By simultaneously monitoring the formation of chemotactic pseudopods at the front of the cell and intracellular Ca2+ concentrations, the authors demonstrated that Ca2+ bursts did not accompany the extension of pseudopods and were only induced when the neutrophil contacted the target or was subjected to supraphysiological concentrations of the anaphylatoxin C5a. Thus, Ca2+ bursts, although potentially important for migration on a substrate or phagocytosis, are not required for neutrophils to sense and initiate a response to chemoattractants.


Global bursts in free intracellular calcium (Ca2+) are among the most conspicuous signaling events in immune cells. To test the common view that Ca2+ bursts mediate rearrangement of the actin cytoskeleton in response to the activation of G protein–coupled receptors, we combined single-cell manipulation with fluorescence imaging and monitored the Ca2+ concentration in individual human neutrophils during complement-mediated chemotaxis. By decoupling purely chemotactic pseudopod formation from cell-substrate adhesion, we showed that physiological concentrations of anaphylatoxins, such as C5a, induced nonadherent human neutrophils to form chemotactic pseudopods but did not elicit Ca2+ bursts. By contrast, pathological or supraphysiological concentrations of C5a often triggered Ca2+ bursts, but pseudopod protrusion stalled or reversed in such cases, effectively halting chemotaxis, similar to sepsis-associated neutrophil paralysis. The maximum increase in cell surface area during pseudopod extension in pure chemotaxis was much smaller—by a factor of 8—than the known capacity of adherent human neutrophils to expand their surface. Because the measured rise in cortical tension was not sufficient to account for this difference, we attribute the limited deformability to a reduced ability of the cytoskeleton to generate protrusive force in the absence of cell adhesion. Thus, we hypothesize that Ca2+ bursts in neutrophils control a mechanistic switch between two distinct modes of cytoskeletal organization and dynamics. A key element of this switch appears to be the expedient coordination of adhesion-dependent lock or release events of cytoskeletal membrane anchors.

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