A chemotaxis model to explain WHIM neutrophil accumulation in the bone marrow of WHIM mouse model.

Autor:	Yip AK; Bioinformatics Institute (BII), A∗STAR (Agency for Science, Technology and Research), Biopolis, 138671 Singapore., Balachander A; Singapore Immunology Network (SIgN), A∗STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Tan LDL; Singapore Immunology Network (SIgN), A∗STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Liong KH; Singapore Immunology Network (SIgN), A∗STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore., Tan RZ; Singapore Institute of Technology, Dover Drive, 138683 Singapore., Balabanian K; INSERM UMR-S996, Laboratory of Excellence in Research on Medication and Innovative Therapeutics, Université Paris-Sud, 92140 Clamart, France., Bachelerie F; INSERM UMR-S996, Laboratory of Excellence in Research on Medication and Innovative Therapeutics, Université Paris-Sud, 92140 Clamart, France., Ng LG; Singapore Immunology Network (SIgN), A∗STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore.; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, 288 Nanjing Road, Tianjin 300020, China., Chiam KH; Bioinformatics Institute (BII), A∗STAR (Agency for Science, Technology and Research), Biopolis, 138671 Singapore.
Jazyk:	angličtina
Zdroj:	Blood science (Baltimore, Md.) [Blood Sci] 2019 Sep 17; Vol. 1 (1), pp. 102-112. Date of Electronic Publication: 2019 Sep 17 (Print Publication: 2019).
DOI:	10.1097/BS9.0000000000000019
Abstrakt:	Neutrophils are essential immune cells that defend the host against pathogenic microbial agents. Neutrophils are produced in the bone marrow and are retained there through CXCR4-CXCL12 signaling. However, patients with the Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome are prone to infections due to increased accumulation of neutrophils in the bone marrow leading to low numbers of circulating neutrophils. How neutrophils accumulate in the bone marrow in this condition is poorly understood. To better understand factors involved in neutrophil accumulation in the bone marrow, neutrophils from wildtype and WHIM mouse models were characterized in their response to CXCL12 stimulation. WHIM neutrophils were found to exert stronger traction forces, formed significantly more lamellipodia-type protrusions and migrated with increased speed and displacement upon CXCL12 stimulation as compared to wildtype cells. Migration speed of WHIM neutrophils showed a larger initial increase upon CXCL12 stimulation, which decayed over a longer time period as compared to wildtype cells. We proposed a computational model based on the chemotactic behavior of neutrophils that indicated increased CXCL12 sensitivity and prolonged CXCR4 internalization adaptation time in WHIM neutrophils as being responsible for increased accumulation in the bone marrow. These findings provide a mechanistic understanding of bone marrow neutrophil accumulation in WHIM condition and novel insights into restoring neutrophil regulation in WHIM patients. Competing Interests: Conflicts of interest: The authors declare no conflicts of interest. (Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the Chinese Association for Blood Sciences.)
Databáze:	MEDLINE
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