The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Human Neutrophils Coordinate Chemotaxis by Differential Activation of Rac1 and Rac2
Abstract
Rac1 and Rac2, members of the small Rho GTPase family, play essential roles in coordinating directional migration and superoxide production during neutrophil responses to chemoattractants. Although earlier studies in Rac1 and Rac2 knockout mice have demonstrated unique roles for each Rac isoform in chemotaxis and NADPH oxidase activation, it is still unclear how human neutrophils use Rac1 and Rac2 to achieve their immunological responses to foreign agent stimulation. In the current study, we used TAT dominant-negative Rac1-T17N and Rac2-T17N fusion proteins to acutely alter the activity of Rac1 and Rac2 individually in human neutrophils. We demonstrate distinct activation kinetics and different roles for Rac1 and Rac2 in response to low vs high concentrations of fMLP. These observations were verified using neutrophils from mice in which Rac1 or Rac2 was genetically absent. Based on these results, we propose a model to explain how human neutrophils kill invading microbes while limiting oxidative damage to the adjacent surrounding healthy tissue through the differential activation of Rac1 and Rac2 in response to different concentrations of chemoattractant.
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“while Rac1 and 2 deficient neutrophils are characterized by an even more pronounced phenotype, supporting the notion that Rac1 and 2 display both redundant and unique roles in neutrophils64,65.”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [64]
In the citing paper
“Interestingly, migration and oxidase production in response to fMLP are normal in Rac1−/− neutrophils”
From Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders (2013) · cites this paper as [64]
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Citations
Cites
Rac and Cdc42 GTPases control hematopoietic stem cell shape, adhesion, migration, and mobilization
Yang, F.-C., Atkinson, S. J., Gu, Y., Borneo, J. B., Roberts, A. W., Zheng, Y., Pennington, J., & Williams, D. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.101546898 · Cited by 201
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- 1994, Rac translocates independently of the neutrophil NADPH oxidase components p47phox and p67phox: evidence for its interaction with flavocytochrome b558., 30749
- 1993, Translocation of Rac correlates with NADPH oxidase activation: evidence for equimolar translocation of oxidase components., 20983
- 2008, Mammalian Rho GTPases: new insights into their functions from in vivo studies., 690
- 2003, Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions., 5652
- 2001, Rac2 is an essential regulator of neutrophil nicotinamide adenine dinucleotide phosphate oxidase activation in response to specific signaling pathways., 1223
- 1999, Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense., 183
- 2004, Rac1 is the small GTPase responsible for regulating the neutrophil chemotaxis compass., 3758
- 2007, Rac1 and Rac2 differentially regulate actin free barbed end formation downstream of the fMLP receptor., 239
- 2004, Rac2-deficient murine macrophages have selective defects in superoxide production and phagocytosis of opsonized particles., 5971
- 2002, Chemoattractant-stimulated Rac activation in wild-type and Rac2-deficient murine neutrophils: preferential activation of Rac2 and Rac2 gene dosage effect on neutrophil functions., 5043
- 2006, Rac1 links leading edge and uropod events through Rho and myosin activation during chemotaxis., 2814
- 2005, The role of Rac1 and Rac2 in bacterial killing., 92
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Cited by
Gianni, D., Taulet, N., Zhang, H., DerMardirossian, C., Kister, J., Martinez, L., Roush, W. R., Brown, S. J., Bokoch, G. M., & Rosen, H. (2010) · ACS Chemical Biology · doi:10.1021/cb100219n · Cited by 192
Self-citationPai, S.-Y., Kim, C., & Williams, D. A. (2010) · Disease Markers · doi:10.1155/2010/380291 · Cited by 85
Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders
Troeger, A., & Williams, D. A. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.07.002 · Cited by 73
Metadata
- Authors
- Zhang, H., Sun, C., Glogauer, M., & Bokoch, G. M.
- Affiliations
- Department of Immunology and Microbial Science and Department of Cell Biology, Scripps Research Institute , La Jolla, CA 92037
- Canadian Institutes for Health Research Group in Matrix Dynamics and Dental Research Institute, University of Toronto, Faculty of Dentistry , Toronto, Ontario,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-08
- Volume
- 183
- Issue
- 4
- Pages
- 2718-2728
- ISSN
- 1550-6606
- 0022-1767
- PMC
- PMC3056163
- Cited by
- 50
- References
- 1
- Language
- en
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- Zhang, H., Sun, C., Glogauer, M., & Bokoch, G. M. (2009). Human Neutrophils Coordinate Chemotaxis by Differential Activation of Rac1 and Rac2. The Journal of Immunology. https://doi.org/10.4049/jimmunol.0900849
