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Kinetics of eotaxin generation and its relationship to eosinophil accumulation in allergic airways disease: analysis in a guinea pig model in vivo.

Humbles AA, Conroy DM, Marleau S, Rankin SM, Palframan RT, Proudfoot AE, Wells TN, Li D, Jeffery PK, Griffiths-Johnson DA, Williams TJ, Jose PJ - J. Exp. Med. (1997)

Bottom Line: Immunoreactive eotaxin levels rose in airway tissue and BAL fluid to a peak at 6 h falling to low levels by 12 h.Constitutive eotaxin was present in BAL fluid.Allergen-induced eotaxin appeared to be mainly in airway epithelium and macrophages, as detected by immunostaining.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Pharmacology, Imperial College School of Medicine at the National Heart and Lung Institute, London SW3 6LY, United Kingdom.

ABSTRACT
Challenge of the airways of sensitized guinea pigs with aerosolized ovalbumin resulted in an early phase of microvascular protein leakage and a delayed phase of eosinophil accumulation in the airway lumen, as measured using bronchoalveolar lavage (BAL). Immunoreactive eotaxin levels rose in airway tissue and BAL fluid to a peak at 6 h falling to low levels by 12 h. Eosinophil numbers in the tissue correlated with eotaxin levels until 6 h but eosinophils persisted until the last measurement time point at 24 h. In contrast, few eosinophils appeared in BAL over the first 12 h, major trafficking through the airway epithelium occurring at 12-24 h when eotaxin levels were low. Constitutive eotaxin was present in BAL fluid. Both constitutive and allergen-induced eosinophil chemoattractant activity in BAL fluid was neutralized by an antibody to eotaxin. Allergen-induced eotaxin appeared to be mainly in airway epithelium and macrophages, as detected by immunostaining. Allergen challenge of the lung resulted in a rapid release of bone marrow eosinophils into the blood. An antibody to IL-5 suppressed bone marrow eosinophil release and lung eosinophilia, without affecting lung eotaxin levels. Thus, IL-5 and eotaxin appear to cooperate in mediating a rapid transfer of eosinophils from the bone marrow to the lung in response to allergen challenge.

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Effect of dexamethasone on allergen-induced eosinophil accumulation in (A) BAL and (B) lung tissue. Sensitized guinea pigs were  injected i.p. with dexamethasone (40 mg/kg) or saline at 24 and 1 h before allergen challenge. 0 h represents sensitized/nonchallenged animals  (n = 5). Results are presented as mean±SEM (n = 5–11 allergen-challenged animals/time point) and significant differences between dexamethasone- and saline-treated groups are indicated as *P <0.05 and **P  <0.005. Basal eosinophil numbers in BAL and lung tissue are shown by  the dashed lines.
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Figure 4: Effect of dexamethasone on allergen-induced eosinophil accumulation in (A) BAL and (B) lung tissue. Sensitized guinea pigs were injected i.p. with dexamethasone (40 mg/kg) or saline at 24 and 1 h before allergen challenge. 0 h represents sensitized/nonchallenged animals (n = 5). Results are presented as mean±SEM (n = 5–11 allergen-challenged animals/time point) and significant differences between dexamethasone- and saline-treated groups are indicated as *P <0.05 and **P <0.005. Basal eosinophil numbers in BAL and lung tissue are shown by the dashed lines.

Mentions: Fig. 4 shows the effects of dexamethasone pretreatment on eosinophil accumulation in the lungs of sensitized/ovalbumin-challenged animals. The glucocorticoid markedly suppressed eosinophil accumulation in lung tissue and virtually eliminated their appearance in the BAL. However, as shown in Fig. 5, this effect was not the result of suppression of eotaxin generation, dexamethasone having no significant effect on levels of immunoreactive eotaxin.


Kinetics of eotaxin generation and its relationship to eosinophil accumulation in allergic airways disease: analysis in a guinea pig model in vivo.

Humbles AA, Conroy DM, Marleau S, Rankin SM, Palframan RT, Proudfoot AE, Wells TN, Li D, Jeffery PK, Griffiths-Johnson DA, Williams TJ, Jose PJ - J. Exp. Med. (1997)

Effect of dexamethasone on allergen-induced eosinophil accumulation in (A) BAL and (B) lung tissue. Sensitized guinea pigs were  injected i.p. with dexamethasone (40 mg/kg) or saline at 24 and 1 h before allergen challenge. 0 h represents sensitized/nonchallenged animals  (n = 5). Results are presented as mean±SEM (n = 5–11 allergen-challenged animals/time point) and significant differences between dexamethasone- and saline-treated groups are indicated as *P <0.05 and **P  <0.005. Basal eosinophil numbers in BAL and lung tissue are shown by  the dashed lines.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199038&req=5

Figure 4: Effect of dexamethasone on allergen-induced eosinophil accumulation in (A) BAL and (B) lung tissue. Sensitized guinea pigs were injected i.p. with dexamethasone (40 mg/kg) or saline at 24 and 1 h before allergen challenge. 0 h represents sensitized/nonchallenged animals (n = 5). Results are presented as mean±SEM (n = 5–11 allergen-challenged animals/time point) and significant differences between dexamethasone- and saline-treated groups are indicated as *P <0.05 and **P <0.005. Basal eosinophil numbers in BAL and lung tissue are shown by the dashed lines.
Mentions: Fig. 4 shows the effects of dexamethasone pretreatment on eosinophil accumulation in the lungs of sensitized/ovalbumin-challenged animals. The glucocorticoid markedly suppressed eosinophil accumulation in lung tissue and virtually eliminated their appearance in the BAL. However, as shown in Fig. 5, this effect was not the result of suppression of eotaxin generation, dexamethasone having no significant effect on levels of immunoreactive eotaxin.

Bottom Line: Immunoreactive eotaxin levels rose in airway tissue and BAL fluid to a peak at 6 h falling to low levels by 12 h.Constitutive eotaxin was present in BAL fluid.Allergen-induced eotaxin appeared to be mainly in airway epithelium and macrophages, as detected by immunostaining.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Pharmacology, Imperial College School of Medicine at the National Heart and Lung Institute, London SW3 6LY, United Kingdom.

ABSTRACT
Challenge of the airways of sensitized guinea pigs with aerosolized ovalbumin resulted in an early phase of microvascular protein leakage and a delayed phase of eosinophil accumulation in the airway lumen, as measured using bronchoalveolar lavage (BAL). Immunoreactive eotaxin levels rose in airway tissue and BAL fluid to a peak at 6 h falling to low levels by 12 h. Eosinophil numbers in the tissue correlated with eotaxin levels until 6 h but eosinophils persisted until the last measurement time point at 24 h. In contrast, few eosinophils appeared in BAL over the first 12 h, major trafficking through the airway epithelium occurring at 12-24 h when eotaxin levels were low. Constitutive eotaxin was present in BAL fluid. Both constitutive and allergen-induced eosinophil chemoattractant activity in BAL fluid was neutralized by an antibody to eotaxin. Allergen-induced eotaxin appeared to be mainly in airway epithelium and macrophages, as detected by immunostaining. Allergen challenge of the lung resulted in a rapid release of bone marrow eosinophils into the blood. An antibody to IL-5 suppressed bone marrow eosinophil release and lung eosinophilia, without affecting lung eotaxin levels. Thus, IL-5 and eotaxin appear to cooperate in mediating a rapid transfer of eosinophils from the bone marrow to the lung in response to allergen challenge.

Show MeSH
Related in: MedlinePlus