Eosinophil accumulation in postnatal lung is specific to the primary septation phase of development

Levels of interleukin (IL)-13 are increased in asthmatic airways. IL-13 has been shown to be necessary and sufficient for allergen-induced airway hyperresponsiveness and increased inflammatory cell counts in bronchoalveolar lavage (BAL) fluid in a murine model of asthma but is thought to protect against airway inflammation when low doses are provided to the guinea pig lung. To determine the role of IL-13 in the guinea pig, we studied the effects of a 360-μg/kg dose of nebulized IL-13 in naive animals and of IL-13 abrogation after airway challenge of sensitized animals. Nebulized IL-13 significantly decreased the dose of histamine required to double baseline respiratory system resistance (ED100, 22 ± 3 vs. 13 ± 2 nmol/kg; P < 0.05) and was associated with recovery of significantly greater numbers of macrophages, lymphocytes, eosinophils, and neutrophils in BAL fluid. Guinea pigs pretreated with a fusion protein that binds IL-13 [soluble IL-13 receptor α2 (sIL-13Rα2)] were protected from developing antigen-induced airway hyperresponsiveness (ED100, 210 ± 50 vs. 20 ± 10 nmol/kg; P <0.01). sIL-13Rα2 (2 doses of 20 mg/kg) significantly reduced the histological grade of allergen-induced lung eosinophil accumulation, whereas the effects of two doses of 10 mg/kg were not significant. These findings demonstrate that the tissue levels of IL-13 induced by allergen challenge of sensitized animals induce airway hyperresponsiveness and inflammation and that IL-13 is required for the expression of allergen-induced airway hyperresponsiveness in the guinea pig ovalbumin model.

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Protein tyrosine phosphatase 11 acts through RhoA/ROCK to regulate eosinophil accumulation in the allergic airway

The FASEB Journal ◽

10.1096/fj.201900698r ◽

2019 ◽

Vol 33 (11) ◽

pp. 11706-11720 ◽

Cited By ~ 5

Author(s):

Chengyun Xu ◽

Xiling Wu ◽

Meiping Lu ◽

Lanfang Tang ◽

Hongyi Yao ◽

...

Keyword(s):

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Protein Tyrosine ◽

Eosinophil Accumulation

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Selectins mediate eosinophil recruitment in vivo: a comparison with their role in neutrophil influx

Blood ◽

10.1182/blood.v87.12.5297.bloodjournal87125297 ◽

1996 ◽

Vol 87 (12) ◽

pp. 5297-5304 ◽

Cited By ~ 26

Author(s):

GM Henriques ◽

JM Miotla ◽

SB Cordeiro ◽

BA Wolitzky ◽

ST Woolley ◽

...

Keyword(s):

Monoclonal Antibody ◽

Adhesion Molecule ◽

Functional Redundancy ◽

Neutrophil Recruitment ◽

Eosinophil Recruitment ◽

Neutrophil Influx ◽

Eosinophil Accumulation

The role of selectins in mediating eosinophil recruitment in vivo was assessed in a model of lipopolysaccharide (LPS)-induced mouse pleurisy. LPS administration resulted in significant eosinophil influx at 24 hours, whereas neutrophil recruitment to the cavity peaked at 4 hours and persisted for 24 hours. The anti-L-selectin monoclonal antibody (MoAb) MEL-14 effectively inhibited (by 97%) eosinophil influx at 24 hours and also inhibited neutrophil recruitment at both times (75% to 95%). Eosinophil recruitment was partially reduced (54%) by the anti-P- selectin MoAb 5H1 but, in contrast, was unaffected by the anti-E- selectin MoAb 10E6. Neutrophil influx at 4 or 24 hours was not affected by the anti-P- or anti-E-selectin MoAbs. However, coadministration of anti-P-selectin and anti-E-selectin was very effective at inhibiting eosinophil influx at 24 hours (86%) and neutrophil influx at 4 (93%) and 24 hours (92%). These results show that all three selectins play a role in LPS-induced eosinophil and neutrophil recruitment in vivo, although P- and E-selectin show a degree of functional redundancy. The demonstration that P-selectin mediates eosinophil but not neutrophil influx suggests that suppressing the function of this adhesion molecule may be beneficial in blocking eosinophil accumulation in pleural inflammation.

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VCAM-1 has a tissue-specific role in mediating interleukin-4–induced eosinophil accumulation in rat models: evidence for a dissociation between endothelial-cell VCAM-1 expression and a functional role in eosinophil migration

Blood ◽

10.1182/blood.v96.10.3601 ◽

2000 ◽

Vol 96 (10) ◽

pp. 3601-3609 ◽

Cited By ~ 17

Author(s):

Karen Y. Larbi ◽

Andrew R. Allen ◽

Frederick W. K. Tam ◽

Dorian O. Haskard ◽

Roy R. Lobb ◽

...

Keyword(s):

Endothelial Cell ◽

Functional Role ◽

Interleukin 4 ◽

Tissue Specific ◽

Rat Models ◽

Eosinophil Migration ◽

Cell Adhesion Molecule 1 ◽

Dose Dependent ◽

Eosinophil Accumulation

Abstract Eosinophil accumulation has been associated with the pathogenesis of numerous allergic inflammatory disorders. Despite the great interest in this response, many aspects of eosinophil accumulation remain unknown. This is particularly true with respect to tissue-specific mechanisms that may regulate the accumulation of eosinophils in different organs. This study addressed this issue by investigating and comparing the roles of α4-integrins and vascular cell adhesion molecule 1 (VCAM-1) adhesion pathways in interleukin 4 (IL-4)–induced eosinophil accumulation in 2 different rat models of inflammation, namely pleural and cutaneous inflammation. Similar to our previous findings in studies in rat skin, locally administered IL-4 induced a time- and dose-dependent accumulation of eosinophils in rat pleural cavities, a response that was associated with generation of the chemokine eotaxin. The IL-4–induced eosinophil accumulation in skin and pleural cavities was totally inhibited by an antirat α4-integrins monoclonal antibody (mAb) (TA-2). In contrast, whereas an antirat VCAM-1 mAb (5F10) totally blocked the response in skin, IL-4–induced eosinophil accumulation in rat pleural cavities was not affected by VCAM-1 blockade. A radiolabeled mAb technique demonstrated that endothelial-cell VCAM-1 expression was induced in response to IL-4 in both skin and pleural membrane. The results indicate that although endothelial-cell VCAM-1 is present in skin and pleura, a functional role for it in IL-4–induced eosinophil accumulation was evident only in skin. These findings suggest the existence of tissue-specific adhesive mechanisms in regulating leukocyte migration in vivo and demonstrate a dissociation between VCAM-1 expression and eosinophil accumulation.

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