Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammation

Sanctis, George T. De; MacLean, James A.; Qin, Shixin; Wolyniec, Walter W.; Grasemann, Hartmut; Yandava, Chandri; Jiao, Aiping; Noonan, T. C.; Stein‐Streilein, Joan; Green, Francis H. Y.; Drazen, Jeffrey M.

doi:10.1172/jci4017

Cited by 35 publications

(20 citation statements)

References 55 publications

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“…However, despite reports that B cell numbers are elevated in CXCR2 Ϫ/Ϫ mice (18), there was no effect of CXCR2 deficiency on production of these isotypes in response to parasite Ags. Interestingly, total serum IgE was significantly elevated in CXCR2 Ϫ/Ϫ mice ( p ϭ 0.014), consistent with previous observations in a model of airway hyperresponsiveness (10). However, given that neutrophils do not express either high or low affinity IgE receptors (22), it is unlikely that differences in the systemic response of these mice contribute to the marked impairment of neutrophil infiltration and corneal opacification in CXCR2 Ϫ/Ϫ mice.…”

Section: Impaired Neutrophil Infiltration In Cxcr2supporting

confidence: 88%

“…The selective effect of CXCR2 deficiency on neutrophils rather than on eosinophils is similar to an OVA model of airway hyperresponsiveness in which neutrophil recruitment to the lungs was reduced in CXCR2 Ϫ/Ϫ mice, but there was no effect on eosinophil infiltration (10). Expression of IL-8Rs on human eosinophils has been reported (35,36), although a recent study suggests that those findings may have been due to neutrophil contamination (37).…”

Section: Corneas Of Cxcr2mentioning

confidence: 60%

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CXC Chemokine Receptor 2 But Not C-C Chemokine Receptor 1 Expression Is Essential for Neutrophil Recruitment to the Cornea in Helminth-Mediated Keratitis (River Blindness)

Hall

Diaconu

Patel

et al. 2001

The Journal of Immunology

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Infiltration of neutrophils and eosinophils into the mammalian cornea can result in loss of corneal clarity and severe visual impairment. To identify mediators of granulocyte recruitment to the corneal stroma, we determined the relative contribution of chemokine receptors CXC chemokine receptor (CXCR)-2 (IL-8R homologue) and CCR1 using a murine model of ocular onchocerciasis (river blindness) in which neutrophils and eosinophils migrate from peripheral vessels to the central cornea. CXCR2−/− and CCR1−/− mice were immunized s.c. and injected into the corneal stroma with Ags from the parasitic helminth Onchocerca volvulus. We found that production of macrophage-inflammatory protein (MIP)-2, KC, and MIP-1α was localized to the corneal stroma, rather than to the epithelium, which was consistent with the location of neutrophils in the cornea. CCR1 deficiency did not inhibit neutrophil or eosinophil infiltration to the cornea or development of corneal opacification. In marked contrast, neutrophil recruitment to the corneas of CXCR2−/− mice was significantly impaired (p < 0.0001 compared with control, BALB/c mice) with only occasional neutrophils detected in the central cornea. Furthermore, CXCR2−/− mice developed only mild corneal opacification compared with BALB/c mice. These differences were not due to impaired KC and MIP-2 production in the corneal stroma of CXCR2−/− mice, which was similar to BALB/c mice. Furthermore, although MIP-1α production was lower in CXCR2−/− mice than BALB/c mice, eosinophil recruitment to the cornea was not impaired. These observations demonstrate the critical role for CXCR2 expression in neutrophil infiltration to the cornea and may indicate a target for immune intervention in neutrophil-mediated corneal inflammation.

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Section: Impaired Neutrophil Infiltration In Cxcr2supporting

confidence: 88%

Section: Corneas Of Cxcr2mentioning

confidence: 60%

CXC Chemokine Receptor 2 But Not C-C Chemokine Receptor 1 Expression Is Essential for Neutrophil Recruitment to the Cornea in Helminth-Mediated Keratitis (River Blindness)

Hall

Diaconu

Patel

et al. 2001

The Journal of Immunology

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“…Therefore, it appears that CXCR2 functions in nematode infections, as it does in other infections (9,18), as a crucial factor for neutrophil recruitment.…”

Section: Vol 74 2006 Eosinophils and Neutrophils In Protective Immumentioning

confidence: 99%

“…The requirement for eosinophils in protective immunity was tested by eliminating these cells from naïve and immunized mice with the anti-CCR3 MAb. Likewise, the necessity for neutrophils was tested in CXC receptor 2 knockout (CXCR2 Ϫ/Ϫ ) mice, which are deficient in the IL-8 receptor homologue and have a significant defect in neutrophil recruitment but normal eosinophil responses (9,18). Using this series of experiments the relative roles of both eosinophils and neutrophils in innate and adaptive protective immunity were determined.…”

mentioning

confidence: 99%

Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

et al. 2006

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The goal of this study was to determine the roles of eosinophils and neutrophils in innate and adaptive protective immunity to larval Strongyloides stercoralis in mice. The experimental approach used was to treat mice with an anti-CCR3 monoclonal antibody to eliminate eosinophils or to use CXCR2 ؊/؊ mice, which have a severe neutrophil recruitment defect, and then determine the effect of the reduction or elimination of the particular cell type on larval killing. It was determined that eosinophils killed the S. stercoralis larvae in naïve mice, whereas these cells were not required for the accelerated killing of larvae in immunized mice. Experiments using CXCR2؊/؊ mice demonstrated that the reduction in recruitment of neutrophils resulted in significantly reduced innate and adaptive protective immunity. Protective antibody developed in the immunized CXCR2 ؊/؊ mice, thereby demonstrating that neutrophils were not required for the induction of the adaptive protective immune response. Moreover, transfer of neutrophil-enriched cell populations recovered from either wild-type or CXCR2؊/؊ mice into diffusion chambers containing larvae demonstrated that larval killing occurred with both cell populations when the diffusion chambers were implanted in immunized wild-type mice.

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“…The slides were stained with Diff-Quik ® (Dade Behring, Newark, DE). For the instillation of a recombinant tryptase or vehicle control into the lungs, mice were anesthetized with an intramuscular injection of ketamine hydrochloride (40 -60 mg/kg) and xylazine (5-10 mg/kg) (35,36). When an acceptable stage of anesthesia was achieved, the area was disinfected with an iodine-based antiseptic, and a midline incision of the neck was performed to expose the trachea.…”

Section: Generation Of Recombinant Human Tryptases ␣ and ␤I And Analymentioning

confidence: 99%

Evaluation of the Substrate Specificity of Human Mast Cell Tryptase βI and Demonstration of Its Importance in Bacterial Infections of the Lung

Huang¹,

Sanctis²,

O’Brien³

et al. 2001

Journal of Biological Chemistry

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139

132

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Human pulmonary mast cells (MCs) express tryptases ␣ and ␤I, and both granule serine proteases are exocytosed during inflammatory events. Recombinant forms of these tryptases were generated for the first time to evaluate their substrate specificities at the biochemical level and then to address their physiologic roles in pulmonary inflammation. Analysis of a tryptase-specific, phage display peptide library revealed that tryptase ␤I prefers to cleave peptides with 1 or more Pro residues flanked by 2 positively charged residues. Although recombinant tryptase ␤I was unable to activate cultured cells that express different types of protease-activated receptors, the numbers of neutrophils increased >100-fold when enzymatically active tryptase ␤I was instilled into the lungs of mice. In contrast, the numbers of lymphocytes and eosinophils in the airspaces did not change significantly. More important, the tryptase ␤I-treated mice exhibited normal airway responsiveness. Neutrophils did not extravasate into the lungs of tryptase ␣-treated mice. Thus, this is the first study to demonstrate that the two nearly identical human MC tryptases are functionally distinct in vivo. When MCdeficient W/W v mice were given enzymatically active tryptase ␤I or its inactive zymogen before pulmonary infection with Klebsiella pneumoniae, tryptase ␤I-treated W/W v mice had fewer viable bacteria in their lungs relative to zymogen-treated W/W v mice. Because neutrophils are required to combat bacterial infections, human tryptase ␤I plays a critical role in the antibacterial host defenses of the lung by recruiting neutrophils in a manner that does not alter airway reactivity.

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Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammation

Cited by 35 publications

References 55 publications

CXC Chemokine Receptor 2 But Not C-C Chemokine Receptor 1 Expression Is Essential for Neutrophil Recruitment to the Cornea in Helminth-Mediated Keratitis (River Blindness)

CXC Chemokine Receptor 2 But Not C-C Chemokine Receptor 1 Expression Is Essential for Neutrophil Recruitment to the Cornea in Helminth-Mediated Keratitis (River Blindness)

Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

Evaluation of the Substrate Specificity of Human Mast Cell Tryptase βI and Demonstration of Its Importance in Bacterial Infections of the Lung

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