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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on December 3, 2004; DOI: 10.1124/jpet.104.078147

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Enilton A. Camargo
Marcelo N. Muscara
Gilberto De Nucci
Edson Antunes
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Received for publication September 24, 2004.
Revised December 2, 2004.
Accepted for publication December 2, 2004.

Mechanisms Involved in the Enhancement of Allergic Airways Neutrophil Influx by Permanent C-fibers Degeneration in Rats

Carla F. Franco-Penteado 1, Ivani A. Desouza 1, Enilton A. Camargo 1, Simone A. Teixeira 2, Marcelo N. Muscara 2, Gilberto De Nucci 1, Edson Antunes 1*

1 State University of Campinas (UNICAMP) 2 University of Sao Paulo (USP)

* Address correspondence to: E-mail: edson.antunes{at}uol.com.br

Abstract

This study was undertaken to clarify the mechanisms involved in the protective role exerted by C-fibers in the rat lungs. Rats were treated with capsaicin at neonatal stages and immunized with ovalbumin (OVA) at adult ages. Challenge of capsaicin-pretreated rats with OVA promoted a higher influx of neutrophils in bronchoalveolar lavage (BAL) fluid compared with the vehicle group. No significant differences were found for the other cell types. The increased adhesion of fMLP (0.1 µM) and PMA (1 µM)-treated neutrophils to fibronectin-coated wells did not differ among vehicle- and capsaicin-pretreated rats. Additionally, fMLP (10 µM), PAF (0.1 µM) and substance P (50 µM) induced a significant neutrophil chemotaxis, but no differences were found among vehicle and capsaicin groups. Increased levels of TNF-{alpha}, IL-6, IL-10 and LTB4 in BAL fluid as well as higher expression of CINC-3 in lung homogenates were detected in the capsaicin group compared with vehicle group. In the capsaicin group, chronic treatment with compound 48/80 restored the TNF-{alpha} levels to control values and prevented the neutrophil influx in BAL fluid. The enhanced production of TNF-{alpha}, superoxide anion and nitrite by isolated alveolar macrophages in response to LPS (3 µg/ml), PMA (10 nM) and/or zymosan (100 particles/cell) did not differ between vehicle- and capsaicin-pretreated rats. In conclusion, chronic neuropeptide depletion promoted by neonatal capsaicin treatment in rats up-regulates airways mast cells, which upon activation by antigen at adult ages, release large amounts of cytokines such as TNF-{alpha} and CINC-3 that accounts for the massive airways neutrophil infiltration.


Key words: C-fibers, Capsaicin, Cytokines, Lung, Mast cells, Neutrophils


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