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- W2076193792 abstract "Macrophages are an important component of the innate immune response and their ability to migrate toward pathogens is critical to their success as first responders. Several proteins are known to contribute to the migration of macrophages and their roles have been studied using Boyden chambers, Dunn chambers, and micropipette pointsources. However, visualizing macrophage migration has been difficult due to their inherently strong adhesion. We have been able to study macrophage migration in two dimensions using a novel surface preparation in which PDMS coated coverslips are stamped with the extracellular matrix protein fibronectin. LR5 macrophages were individually tracked on these surfaces in the presence of CSF-1, a physiologically relevant chemokine, using time-lapse microscopy. Analysis of the trajectories of motion has allowed us to describe motility in terms of speed, persistence time, and the random motility coefficient. LR5 cells in which endogenous Cdc42 or WASp was reduced using small interfering RNA were also examined to determine the role of these proteins in migration. Our results indicate that reduction of WASp levels leads to a significant reduction in motility. The knockdown of Cdc42 leads to a reduction in the random motility coefficient and sensitivity to ligand chemistry. Our results are in contrast to other studies which have linked Cdc42 and WASp to directional sensing but have found no defect in random motility. The roles of PI3K in macrophage migration are currently being investigated. We are also beginning to study the forces macrophages produce while migrating using microfabricated post array detectors. The cell lines with reduced protein levels will also be studied on posts to determine the role of each protein in force production." @default.
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- W2076193792 date "2013-01-01" @default.
- W2076193792 modified "2023-09-27" @default.
- W2076193792 title "Macrophage Migration and the Roles of WASP, Cdc42, and PI3K" @default.
- W2076193792 doi "https://doi.org/10.1016/j.bpj.2012.11.1778" @default.
- W2076193792 hasPublicationYear "2013" @default.
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