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Journal article
Dual Roles for Rac2 in Neutrophil Motility and Active Retention in Zebrafish Hematopoietic Tissue
Developmental cell, Vol.21(4), pp.735-745
10/18/2011
PMCID: PMC3199325
PMID: 22014524
Web of Science ID: WOS:000296366000016
Abstract
Neutrophil homeostasis is essential for host defense. Here we identify dual roles for Rac2 during neutrophil homeostasis using a zebrafish model of primary immune deficiency induced by the human inhibitory Rac2D57N mutation in neutrophils. Noninvasive live imaging of Rac2 morphants or Rac2D57N zebrafish larvae demonstrates an essential role for Rac2 in regulating 3D motility and the polarization of F-actin dynamics and PI(3)K signaling in vivo. Tracking of photolabeled Rac2-deficient neutrophils from hematopoietic tissue also shows increased mobilization into the circulation, indicating that neutrophil mobilization does not require traditionally defined cell motility. Moreover, excessive neutrophil retention in hematopoietic tissue resulting from a constitutively active CXCR4 mutation in zebrafish warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is partially rescued by the inhibitory Rac2 mutation. These findings reveal that Rac2 signaling is necessary for both neutrophil 3D motility and CXCR4-mediated neutrophil retention in hematopoietic tissue, thereby limiting neutrophil mobilization, a critical first step in the innate immune response.
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- Title
- Dual Roles for Rac2 in Neutrophil Motility and Active Retention in Zebrafish Hematopoietic Tissue
- Publication Details
- Developmental cell, Vol.21(4), pp.735-745
- Resource Type
- Journal article
- Publisher
- Elsevier
- Format
- pdf
- Number of pages
- 11
- Grant note
- Burroughs Wellcome fund; Burroughs Wellcome Fund GM074827 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM074827 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Identifiers
- WOS:000296366000016; 99380171296206600
- Academic Unit
- Biology; Hal Marcus College of Science and Engineering
- Language
- English