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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: Constitutive eotaxin was present in BAL fluid.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.

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 an anti–IL-5 antibody, TRFK5, on eosinophil numbers in (A) BAL and (B) lung tissue, and eotaxin levels in (C) BAL fluid and (D)  lung tissue after allergen challenge. Sensitized guinea pigs were injected i.v. with control rat IgG or TRFK5 (0.3 mg/kg) 30 min before aerosol exposure  to saline or allergen. Results are presented as mean±SEM (n = 5–6 animals/group) and significant differences between control IgG and TRFK5-treated  groups are indicated as *P <0.05 and **P <0.005.
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Figure 6: Effect of an anti–IL-5 antibody, TRFK5, on eosinophil numbers in (A) BAL and (B) lung tissue, and eotaxin levels in (C) BAL fluid and (D) lung tissue after allergen challenge. Sensitized guinea pigs were injected i.v. with control rat IgG or TRFK5 (0.3 mg/kg) 30 min before aerosol exposure to saline or allergen. Results are presented as mean±SEM (n = 5–6 animals/group) and significant differences between control IgG and TRFK5-treated groups are indicated as *P <0.05 and **P <0.005.

Mentions: In a previous study (16) we found no evidence of eosinophil chemoattractant activity corresponding to IL-5 in BAL fluid from sensitized/ovalbumin-challenged guinea pigs. However, pretreatment of animals with a neutralizing antibody to IL-5, TRFK5, markedly suppressed allergen-induced eosinophil accumulation in lung tissue and BAL in sensitized animals (Fig. 6, A and B). The antibody also significantly reduced eosinophil numbers in the lung tissue of sensitized animals 6 h after aerosolized saline. TRFK5 had no significant effect on the numbers of mononuclear cells or neutrophils in BAL (data not shown) or on the levels of eotaxin in BAL fluid and lung tissue (Fig. 6, C and D).


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 an anti–IL-5 antibody, TRFK5, on eosinophil numbers in (A) BAL and (B) lung tissue, and eotaxin levels in (C) BAL fluid and (D)  lung tissue after allergen challenge. Sensitized guinea pigs were injected i.v. with control rat IgG or TRFK5 (0.3 mg/kg) 30 min before aerosol exposure  to saline or allergen. Results are presented as mean±SEM (n = 5–6 animals/group) and significant differences between control IgG and TRFK5-treated  groups are indicated as *P <0.05 and **P <0.005.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: Effect of an anti–IL-5 antibody, TRFK5, on eosinophil numbers in (A) BAL and (B) lung tissue, and eotaxin levels in (C) BAL fluid and (D) lung tissue after allergen challenge. Sensitized guinea pigs were injected i.v. with control rat IgG or TRFK5 (0.3 mg/kg) 30 min before aerosol exposure to saline or allergen. Results are presented as mean±SEM (n = 5–6 animals/group) and significant differences between control IgG and TRFK5-treated groups are indicated as *P <0.05 and **P <0.005.
Mentions: In a previous study (16) we found no evidence of eosinophil chemoattractant activity corresponding to IL-5 in BAL fluid from sensitized/ovalbumin-challenged guinea pigs. However, pretreatment of animals with a neutralizing antibody to IL-5, TRFK5, markedly suppressed allergen-induced eosinophil accumulation in lung tissue and BAL in sensitized animals (Fig. 6, A and B). The antibody also significantly reduced eosinophil numbers in the lung tissue of sensitized animals 6 h after aerosolized saline. TRFK5 had no significant effect on the numbers of mononuclear cells or neutrophils in BAL (data not shown) or on the levels of eotaxin in BAL fluid and lung tissue (Fig. 6, C and D).

Bottom Line: Constitutive eotaxin was present in BAL fluid.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.

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