Defining a Link with Asthma in Mice Congenitally Deficient in Eosinophils

Abstract

Eosinophils are often dominant inflammatory cells present in the lungs of asthma patients. Nonetheless, the role of these leukocytes remains poorly understood. We have created a transgenic line of mice (PHIL) that are specifically devoid of eosinophils, but otherwise have a full complement of hematopoietically derived cells. Allergen challenge of PHIL mice demonstrated that eosinophils were required for pulmonary mucus accumulation and the airway hyperresponsiveness associated with asthma. The development of an eosinophil-less mouse now permits an unambiguous assessment of a number of human diseases that have been linked to this granulocyte, including allergic diseases, parasite infections, and tumorigenesis.

Hierarchy of eosinophil chemoattractants: role of p38 mitogen‐activated protein kinase

“…Samples of whole blood and leukocytes isolated by dextran sedimentation and washed free from plasma (isolated) were stimulated with agonists. Red blood cells were lysed by NH 4 Cl, and shape change responses were analyzed by flow cytometry as increases in forward scatter of eosinophils and neutrophils. As compared with isolated cells, the potency of 5-oxo-ETE and eotaxin was reduced in whole blood, while the potency of PGD 2 and IL-8 was unchanged.…”

“…Samples of whole blood, and buffy coats suspended in platelet-rich plasma (PRP), platelet-poor plasma (PPP) or phosphate-buffered salt solution (PBS) were stimulated with agonists. Red blood cells were lysed by means of NH 4 Cl and shape change responses were analyzed by flow cytometry as increases in forward scatter of eosinophils and neutrophils. The loss of 5-oxo-ETE bio-activity in whole blood was not reversed by depleting the red blood cells prior to stimulation (buffy coat in PRP) or additional depletion of platelets (buffy coat in PPP), but was prevented in the absence of plasma (buffy coat in PBS).…”

“…It has been shown recently that asthmatic patients that received treatment based on eosinophil counts in sputum had significantly fewer severe asthma exacerbations than patients treated according to standard management therapy [2]. Moreover, genetically modified mice lacking eosinophils are protected against allergen-induced lung injury and asthma [3,4].…”

“…It has been shown recently that asthmatic patients that received treatment based on eosinophil counts in sputum had significantly fewer severe asthma exacerbations than patients treated according to standard management therapy [2]. Moreover, genetically modified mice lacking eosinophils are protected against allergen-induced lung injury and asthma [3,4].Although several chemoattractants can mediate eosinophil recruitment, none of them could be identified so far as a predominating factor governing eosinophil infiltration, suggesting a co-operative action of multiple chemoattractants in disease. Among these are the CC-chemokines, such as eotaxin, RANTES, or MCP-4 acting through the chemokine receptor CCR3 [5,6].…”

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

“…The airway inflammation of asthma has a predominance of Th2 CD4 + lymphocytes, eosinophils and mast cells infiltrating the lung interstitium. Several studies indicate the existence of a mechanism dependent on IL-5 and eosinophils that induce pulmonary damage and intensify AHR [3][4][5]. In other studies, however, the induction of AHR was observed despite the absence of infiltrating eosinophils, suggesting dissociation between these phenomena [6][7][8][9][10].…”