Inhibition of pulmonary eosinophilia does not necessarily prevent the airway hyperresponsiveness induced by Sephadex beads.

Abstract

BACKGROUND:

The Lewis rat among highly inbred strains exhibits significant airway hyperresponsiveness (AHR) following intravenous administration of Sephadex G-200 (Sephadex). The aim of this study was to investigate the association of Sephadex-induced AHR with changes in airway inflammation in Lewis rats.

METHODS:

A suspension (0.5 mg/ml/rat) of Sephadex was intravenously administered to male Lewis rats on days 0, 2 and 5. Measurement of airway responsiveness to serotonin, bronchoalveolar lavage (BAL) and histological study were performed on day 2-11.

RESULTS:

Significant AHR induced by Sephadex was recognized on day2 (p < 0.05), and AHR reached a maximum on day 7 (p < 0.001). In the BAL study, eosinophils increased on day2 (p < 0.01) with a peak on day 5 (p < 0.05). In the histological study, we found Sephadex beads trapped in small arteries of the lung and granulomatous arteritis on day 2 or later. Pulmonary granulomas, horseshoe-shaped multinuclear giant cells, eosinophils and goblet cell hyperplasia were observed on day 2, and the degree became intense on day 5-7. GCC-AP0341 (10 mg/kg, i.p. x 3) inhibited the recruitment of eosinophils in BAL fluid and in lung tissue, but it did not inhibit AHR. The compound also inhibited pulmonary granulomas and goblet cell hyperplasia.

CONCLUSION:

The mechanism of Sephadex-induced AHR may not be directly associated with inflammatory changes such as recruitment of eosinophils, pulmonary granulomas and hyperplasia of goblet cells in rats.

• Authors: S Matsubara, K Fushimi, K Ogawa, H Kikkawa, A Nakata, R Kameda, M Kikuchi, K Naito, K Ikezawa
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 116 Issue 1 Pg. 67-75 (May 1998) ISSN: 1018-2438 [Print] Switzerland
• PMID: 9623512 (Publication Type: Journal Article)

Chemical References

• Dextrans
• GCC-AP 0341
• Indicators and Reagents
• Proteins
• Triazoles
• sephadex

Topics

• Animals
• Bronchial Hyperreactivity (chemically induced, physiopathology, prevention & control)
• Bronchial Provocation Tests
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Dextrans (administration & dosage, adverse effects)
• Eosinophils (cytology, drug effects, metabolism)
• Indicators and Reagents (administration & dosage, adverse effects)
• Injections, Intravenous
• Leukocytes, Mononuclear (cytology, drug effects, metabolism)
• Male
• Neutrophils (cytology, drug effects, metabolism)
• Pneumonia (drug therapy)
• Proteins (drug effects, metabolism)
• Pulmonary Eosinophilia (physiopathology)
• Rats
• Rats, Inbred Lew
• Time Factors
• Triazoles (administration & dosage, therapeutic use)