Comparison of ciliary activity and inflammatory mediator release from bronchial epithelial cells of nonatopic nonasthmatic subjects and atopic asthmatic patients and the effect of diesel exhaust particles in vitro☆,☆☆,★,★★

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Abstract

Background: Recent studies have suggested that asthmatic patients may be more susceptible to the adverse effects of air pollutants, including diesel exhaust particles (DEP). The underlying mechanisms, however, are not clear. Methods: We cultured bronchial epithelial cells from bronchial biopsy specimens of well-characterized groups of nonatopic, nonasthmatic individuals and atopic patients with mild asthma and compared the ciliary beat frequency (CBF) and release of IL-8, GM-CSF, regulated on activation, normal T-cell expressed and secreted (RANTES), and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells both before and after exposure for 24 hours to 10 to 100 μg/mL DEP in vitro. Results: The baseline CBF was not found to be significantly different in the bronchial epithelial cell cultures of nonasthmatic and asthmatic individuals. Incubation with DEP significantly attenuated the CBF of both the nonasthmatic and asthmatic bronchial epithelial cell cultures at all concentrations of DEP investigated and were maximal (55.5% and 45.2%, respectively) after incubation with 100 μg/mL DEP. The bronchial epithelial cell cultures of asthmatic patients constitutively released significantly greater amounts of IL-8, GM-CSF, and sICAM-1 than bronchial epithelial cell cultures of nonasthmatic subjects. The cultures of only asthmatic patients additionally released RANTES. Incubation of the asthmatic cultures with 10 μg/mL DEP significantly increased the release of IL-8 (from 102.0 to 167.8 pg/μg cellular protein; P < .01), GM-CSF (from 0.43 to 1.87 pg/μg cellular protein; P < .01), and sICAM-1 (from 14.7 to 38.1 pg/μg cellular protein; P < .02) after 24 hours. Incubation with 50 to 100 μg/mL DEP, however, significantly decreased the release of IL-8 and RANTES from these cultures. In contrast, only the higher concentrations of 50 to 100 μg/mL DEP significantly increased release of IL-8 (from 37.9 to 71.5 pg/μg cellular protein; P < .05) and GM-CSF (from 0.06 to 0.34 pg/μg cellular protein; P < .05) from the bronchial epithelial cells of nonasthmatic individuals. Conclusions: These results suggest that bronchial epithelial cells of asthmatic subjects are different from bronchial epithelial cells of nonasthmatic subjects with regard to the amounts and types of proinflammatory mediators they can release and that the increased sensitivity of bronchial epithelial cells of asthmatic subjects to DEP may possibly result in exacerbation of their disease symptoms. (J Allergy Clin Immunol 1998;102:771-82.)

Section snippets

Nonatopic nonasthmatic subjects and atopic asthmatic patients

Twenty-eight volunteers (12 women and 16 men) with a mean age of 29 years (range, 19 to 45 years) took part in the study. Of these, 13 were nonatopic nonasthmatic subjects (control subjects) and 15 were atopic mildly asthmatic patients. The characteristics of these individuals are shown in Table I and demonstrated that there were no significant differences in the age and sex ratios.

. Characteristics of study volunteers

GroupSubjectAge (y)SexAtopy (SPT)PC20 FEV1 (mg/mL)
HDMGPAFDogCat
Nonatopic

RESULTS

These studies have demonstrated that epithelial cells can be grown as explant cultures from bronchial biopsy specimens of well-characterized nonatopic nonasthmatic subjects and atopic asthmatic patients (Fig 1).

. Typical confluent human bronchial epithelial cell culture after 2 to 3 weeks in culture.

The cells reached confluence after 2 to 3 weeks in culture and demonstrated typical polygonal morphology characteristic of epithelial cells. The epithelial nature of the cells was confirmed by

DISCUSSION

These studies have demonstrated that bronchial epithelial cells can be grown as confluent explant cultures from biopsy specimens of well-characterized groups of both atopic asthmatic patients and nonatopic nonasthmatic subjects. Additionally, these studies have demonstrated that the cells of atopic asthmatic patients are different from the cells of nonatopic nonasthmatic subjects, with regard to the quantities and types of specific proinflammatory mediators that they can release constitutively,

Acknowledgements

We thank Janice Thomas (Computer Services Department, St Bartholomew’s Hospital, London) for her advice on the statistical analysis of the data.

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    • Cited by (0)

    ☆

    From a the Academic Department of Respiratory Medicine, St Bartholomew’s and the Royal London School of Medicine and Dentistry, The London Chest Hospital; and the b National Institute for Environmental Studies, Research Team for Health Effects of Air Pollutants, Ibaraki.

    ☆☆

    Supported by the National Asthma Campaign, UK, and the University of Dicle, Turkey (H.B.).

    ★

    Reprint requests: Jagdish L. Devalia, PhD, Academic Department of Respiratory Medicine, St Bartholomew’s and the Royal London School of Medicine and Dentistry, The London Chest Hospital, Bonner Road, London E2 9JX, UK.

    ★★

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