Kinetics of Eotaxin Generation and Its Relationship to Eosinophil Accumulation in Allergic Airways Disease: Analysis in a Guinea Pig Model In Vivo

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.

Critical Role for T Cells in Sephadex-Induced Airway Inflammation: Pharmacological and Immunological Characterization and Molecular Biomarker Identification

“…Likewise, exposure of IL-5 gene knockout mice to aerosolized Ags caused an ablated eosinophil recruitment into the lungs (42). The results from both in vitro and in vivo investigations also suggest that eotaxin and IL-5 may act cooperatively and synergistically to promote the recruitment of eosinophils into tissues (29,30,43,44). In mice, eotaxin-induced recruitment of eosinophils to the lung and skin was only consistently observed in IL-5-transgenic mice, which have elevated levels of IL-5 and a pronounced basal blood eosinophilia (29,30).…”

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

“…There is some limited data. RAN-TES expression has been observed in airway smooth muscle cells in airway bronchial biopsies from healthy volunteers as well as from asthmatic subjects [26], while eotaxin immunoreactivity is reported in airway smooth muscle of airways from patients with asthma, with weaker staining in those from healthy volunteers [32], and of airways from guinea-pigs following allergen challenge [82]. Therefore, the production of chemokines in the airway smooth muscle may allow a gradient of chemotaxis to exist between the microvasculature and the airway smooth muscle, allowing T-cells, eosinophils, neutrophils, and monocytes to accumulate around smooth muscle cells.…”

Arsenic trioxide alleviates airway hyperresponsiveness and eosinophilia in a murine model of asthma

“…24 IL-5 was originally discovered in guinea pigs and found to be responsible for allergen-induced eosinophil accumulation in the lungs. 25 Eotaxin is an eosinophil-selective chemoattractant that has been identified as a potent activator of eosinophils, inducing eosinophils to generate superoxide and release granule proteins. Early studies suggested that eosinophil recruitment in allergic reactions was regulated by Th2 lymphocytes and that eotaxin production was T celldependent.…”