Eotaxin and monocyte chemotactic protein-4 mRNA expression in small airways of asthmatic and nonasthmatic individuals

doi:10.1016/S0091-6749(99)70474-4

Journal of Allergy and Clinical Immunology

Volume 103, Issue 3, March 1999, Pages 476-483

https://doi.org/10.1016/S0091-6749(99)70474-4 Get rights and content

Abstract

Background: Although an eosinophilic infiltrate has been observed in the small airways of asthmatic individuals, the mechanisms responsible for cellular recruitment in the lung periphery remain to be clarified. Eotaxin and monocyte chemotactic protein (MCP)-4 are 2 eosinophil-associated chemokines shown to be upregulated at sites of allergic inflammation. However, their expression within the small airways of asthmatic individuals remains to be elucidated. Objective: We sought to determine the expression of eotaxin and MCP-4 in the peripheral airways and parenchyma of lungs of subjects with asthma and to assess their relationship to the numbers of resident eosinophils. Methods: We examined surgically resected lung tissue from 6 asthmatic and 10 nonasthmatic subjects for the presence of eotaxin and MCP-4 mRNA by in situ hybridization. Chemokine mRNA expression was examined with respect to the numbers of eosinophils within the airways, as detected by immunocytochemistry for major basic protein. Results: Numbers of chemokine mRNA–positive cells were significantly increased in the large and small airways of asthmatic subjects compared with nonasthmatic subjects. Although eotaxin and MCP-4 mRNA were widely expressed in the lungs of subjects with asthma, their expression was particularly evident within the bronchial epithelium and inflammatory cells. In the airways of the asthmatic individuals, the expression of eotaxin mRNA was significantly correlated to the numbers of eosinophils present. Conclusion: There is an increased expression of eotaxin and MCP-4 mRNA within the peripheral airways of lungs of asthmatic subjects, suggesting that these chemokines contribute to the small airways and peripheral lung inflammation in asthma. (J Allergy Clin Immunol 1999;103:476-83.)

Section snippets

Subjects

Lung tissue was obtained from 16 subjects selected from a cohort of 108 individuals entering the St Paul’s Hospital Lung Study between 1991 and 1995. The clinical characteristics of these asthmatic and nonasthmatic patients have been described previously,¹⁶ and they were well matched for age, sex, and cigarette smoking history. Briefly, patients undergoing lung resection for bronchial carcinoma who fulfilled the clinical criteria used to establish a diagnosis of asthma (n = 6) were matched with

RESULTS

Cells positive for eotaxin and MCP-4 mRNA exhibited a dark purple staining within the airways epithelium and submucosa only when the antisense probes for eotaxin and MCP-4 were used. No signals were observed by using the sense probes or from preparations pretreated with RNase. Cells expressing MBP immunoreactivity were quantified by their red cytoplasmic staining, and positive signals were not observed in the presence of an irrelevant primary antibody.

DISCUSSION

The aims of the study were to investigate the expression of eotaxin and MCP-4 mRNA in the large and small airways and lung parenchyma of asthmatic and nonasthmatic individuals. Our results demonstrate an increase in the expression of eotaxin and MCP-4 mRNA within the airways of patients with asthma compared with nonasthmatic control subjects who were matched for age, sex, smoking history, and airway size. We also showed that the numbers of eotaxin mRNA–positive cells were positively correlated

Acknowledgements

We thank Ms Elsa Schotman and Ms Zivart Yasruel for their technical assistance.

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^☆: Supported by the J. T. Costello Memorial Research Fund, the Medical Research Council of Canada, and Inspiraplex. Dr Hamid is a recipient of a Chercheur-Boursier award from the Fonds de la Recherche en Sante du Quebec. Dr Eleanor Minshall is a recipient of a Medical Research Council/Canadian Lung Association Fellowship.

^☆☆: Reprint requests: Qutayba Hamid, MD, PhD, Meakins-Christie Laboratories, McGill University, 3626 St Urbain St, Montreal, Quebec, Canada H2X 2P2.

^★: 0091-6749/99 $8.00 + 0 1/1/95457

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Eotaxin and monocyte chemotactic protein-4 mRNA expression in small airways of asthmatic and nonasthmatic individuals☆,☆☆,★

Abstract

Section snippets

Subjects

RESULTS

DISCUSSION

Acknowledgements

J Allergy Clin Immunol

J Allergy Clin Immunol

Curr Biol

Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma

Am Rev Respir Dis

Airway mucosal inflammation even in patients with newly diagnosed asthma

Am Rev Respir Dis

Predominant Th2-like bronchoalveolar T-lymphocyte population in atopic asthma

N Engl J Med

Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils and basophils induced in allergic and non-allergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3

J Immunol

Molecular cloning and characterisation of a human eotaxin receptor expressed selectively on eosinophils

J Exp Med

High expression of the chemokine receptor CCR3 in human blood basophils

J Clin Invest

Increased expression of eotaxin in bronchoalveolar lavage and airways of asthmatics contributes to the chemotaxis of eosinophils to the site of inflammation

J Immunol

Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells

Eur J Immunol

Eotaxin mRNA and protein expression in chronic sinusitis and allergen-induced nasal responses in seasonal allergic rhinitis

Am J Respir Cell Mol Biol

Monocyte chemotactic protein expression in allergy and non-allergy-associated chronic sinusitis

J Otolaryngol

Expression of eotaxin by human lung epithelial cells: induction by cytokines and inhibition by glucocorticosteroids

J Clin Invest

Production of the novel C-C chemokine MCP-4 by airway cells and comparison of its biological activity to other C-C chemokines

J Clin Invest