NDLI: Convolution of chemoattractant secretion rate, source density, and receptor desensitization direct diverse migration patterns in leukocytes

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Integrative Biology Vol - 5 Issue - 2

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Convolution of chemoattractant secretion rate, source density, and receptor desensitization direct diverse migration patterns in leukocytes

Content Provider	Royal Society of Chemistry (RSC)
Author	Wang, Yana Irvine, Darrell J.
Copyright Year	2013
Abstract	Chemoattractants regulate diverse immunological, developmental, and pathological processes, but how cell migration patterns are shaped by attractant production in tissues remains incompletely understood. Using computational modeling and chemokine-releasing microspheres (CRMs), cell-sized attractant-releasing beads, we analyzed leukocyte migration in physiologic gradients of CCL21or CCL19 produced by beads embedded in 3D collagen gels. Individual T-cells that migrated into contact with CRMs exhibited characteristic highly directional migration to attractant sources independent of their starting position in the gradient (and thus independent of initial gradient strength experienced) but the fraction of responding cells was highly sensitive to position in the gradient. These responses were consistent with modeling calculations assuming a threshold absolute difference in receptor occupancy across individual cells of ∼10 receptors required to stimulate chemotaxis. In sustained gradients eliciting low receptor desensitization, attracted T-cells or dendritic cells swarmed around isolated CRMs for hours. With increasing CRM density, overlapping gradients and high attractant concentrations caused a transition from local swarming to transient “hopping” of cells bead to bead. Thus, diverse migration responses observed in vivo may be determined by chemoattractant source density and secretion rate, which govern receptor occupancy patterns in nearby cells.
Starting Page	481
Ending Page	494
Page Count	14
File Format	HTM / HTML PDF
ISSN	17579694
Volume Number	5
Issue Number	3
Journal	Integrative Biology
DOI	10.1039/c3ib20249f
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Subscribed
Subject Keyword	White blood cell CCL19 Three-dimensional space Collagen Absolute difference Chemotaxis Dendritic cell Swarmed (film)
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Biophysics

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Convolution of chemoattractant secretion rate, source density, and receptor desensitization direct diverse migration patterns in leukocytes