2012
DOI: 10.1182/blood-2012-01-403378
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Proper desensitization of CXCR4 is required for lymphocyte development and peripheral compartmentalization in mice

Abstract: Desensitization controls G protein-dependent signaling of chemokine receptors. We investigate the physiologic implication of this process for CXCR4 in a mouse model harboring a heterozygous mutation of the Cxcr4 gene, which engenders a desensitization-resistant receptor. Such anomaly is linked to the warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome, a human rare combined immunodeficiency. Cxcr4(+/mutant(1013)) mice display leukocytes with enhanced responses to Cxcl12 and exhibit leukopen… Show more

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Cited by 111 publications
(174 citation statements)
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“…axis in regulation of immune cells has been investigated, including a subset of monocytes (i.e., Ly6C high monocytes) (12)(13)(14)(15)(16)(17), whether CXCR4 is involved in regulation of another subset of monocytes (i.e., Ly6C low monocytes) is not known.…”
Section: Significancementioning
confidence: 99%
“…axis in regulation of immune cells has been investigated, including a subset of monocytes (i.e., Ly6C high monocytes) (12)(13)(14)(15)(16)(17), whether CXCR4 is involved in regulation of another subset of monocytes (i.e., Ly6C low monocytes) is not known.…”
Section: Significancementioning
confidence: 99%
“…After incubation with the 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) substrate (Sigma-Aldrich), the reaction was stopped by adding 0.05 M citric acid and 0.01% sodium azide, and the plates were read at OD 405 nm . Total levels of IgG, IgM, and IgA were determined as described previously (32). Serum concentrations of TNF-a, IL-1b, IL-6, and IL-10 were assessed using a standardized ELISA (Quantikine R&D Systems, Rochester, MN).…”
Section: Elisamentioning
confidence: 99%
“…After standardized mechanical dissociation with a gentleMACS Dissociator (Miltenyi Biotec, Bergisch Gladbach, Germany), cells were filtered through a 70-mm-pore nylon mesh (BD Biosciences, San Jose, CA), and erythrocytes were lysed with an ammonium-chloridepotassium buffer. Cells were harvested from mouse spleens as described (32) …”
Section: Leukocyte Preparationmentioning
confidence: 99%
“…5,6 The mechanism appears to involve loss of negative regulatory elements, 7,8 which is thought to increase CXCR4 signaling and the normal adhesion-promoting function of CXCR4 for neutrophils in bone marrow, among other effects. [9][10][11] Granulocyte colony-stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) have been documented to prevent infections in patients with severe congenital neutropenia and hypogammaglobulinemia, respectively. 12,13 Both treatments have been used in WHIM patients; however, no studies have documented clinical efficacy, and they are nonspecific, expensive, difficult to administer, and of questionable efficacy in controlling infections and warts.…”
Section: Introductionmentioning
confidence: 99%