PT  - JOURNAL ARTICLE
AU  - Carla F. Franco-Penteado
AU  - Ivani A. De Souza
AU  - Enilton A. Camargo
AU  - Simone A. Teixeira
AU  - Marcelo N. Muscara
AU  - Gilberto De Nucci
AU  - Edson Antunes
TI  - Mechanisms Involved in the Enhancement of Allergic Airways Neutrophil Influx by Permanent C-Fiber Degeneration in Rats
AID  - 10.1124/jpet.104.078147
DP  - 2005 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 440--448
VI  - 313
IP  - 1
4099  - http://jpet.aspetjournals.org/content/313/1/440.short
4100  - http://jpet.aspetjournals.org/content/313/1/440.full
SO  - J Pharmacol Exp Ther2005 Apr 01; 313
AB  - This study was undertaken to clarify the mechanisms by which C-fiber degeneration at neonatal stages exacerbates the inflammatory responses of rat airways. 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 N-formyl-methionyl-leucyl-phenylalanine (fMLP; 0.1 μM)- and phorbol myristate acetate (PMA; 1 μM)-treated neutrophils to fibronectin-coated wells did not differ among vehicle- and capsaicin-pretreated rats. Additionally, fMLP (10 μM), platelet-activating factor (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 tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and leukotriene B4 in BAL fluid as well as higher expression of cytokine-induced neutrophil chemoattractant (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-α levels to control values and prevented the neutrophil influx in BAL fluid. The enhanced production of TNF-α, superoxide anion, and nitrite by isolated alveolar macrophages in response to lipopolysaccharide (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 up-regulates airways mast cells, which upon activation by antigen at adult ages, release large amounts of cytokines such as TNF-α and CINC-3 that accounts for the massive airways neutrophil infiltration. The American Society for Pharmacology and Experimental Therapeutics