Role of sensory innervation in the rat pulmonary neutrophil recruitment induced by staphylococcal enterotoxins type A and B.
Rat airways exposure to Staphylococcal enterotoxin A (SEA) and B (SEB) induces marked neutrophil influx. Since sensory neuropeptides play important roles in cell infiltration, in this study we have investigated its contribution in triggering SEA- and SEB-induced pulmonary neutrophil infiltration. Male Wistar rats were exposed intratracheally with SEA (3 ng/trachea) or SEB (250 ng/trachea). Animals received different in vivo pretreatments, after which the neutrophil counts and levels of substance P and IL-1 in bronchoalveolar lavage fluid were evaluated. Alveolar macrophages and peritoneal mast cells were incubated with SEA and SEB to determine the IL-1 and TNF-alpha levels. Capsaicin pretreatment significantly reduced SEA- and SEB-induced neutrophil influx in bronchoalveolar lavage fluid, but this treatment was more effective to reduce SEA responses. Treatments with SR140333 (tachykinin NK(1) receptor antagonist) and SR48968 (tachykinin NK(2) receptor antagonist) decreased SEA-induced neutrophil influx, whereas SEB-induced responses were inhibited by SR140333 only. Cyproheptadine (histamine/5-hydroxytriptamine receptor antagonist) and MD 7222 (5-HT(3) receptor antagonist) reduced SEA- and SEB-induced neutrophil influx. The substance P and IL-1 levels in bronchoalveolar lavage fluid of SEA-exposed rats were significantly higher than SEB. In addition, SEA (but not SEB) significantly released mast cell TNF-alpha. Increased production of TNF-alpha and IL-1 in alveolar macrophages was observed in response to SEA and SEB. In conclusion, sensory neuropeptides contribute significantly to SEA- and SEB-induced pulmonary neutrophil recruitment, but SEA requires in a higher extent the airways sensory innervation, and participation of mast cells and alveolar macrophage products.
Department of Pharmacology, State University of Campinas (UNICAMP), Campinas, SP, Brazil. ivanidesouza@fcm.unicamp.br
Ivani A
IA
Desouza
Enilton A
EA
Camargo
Nadia S
NS
Mariano
João B
JB
Optiz-Neto
Jorge S
JS
Resende
Gláucia C
GC
Mello
Soraia K P
SK
Costa
Gilberto
G
De Nucci
Edson
E
Antunes
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002211:Capsaicin / Q000494:pharmacology; D015550:Cell Degranulation; D004768:Enterotoxins / Q000633:toxicity*; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000294:innervation / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D009479:Neuropeptides / Q000172:deficiency / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004768:Enterotoxins; D053583:Interleukin-1beta; D009479:Neuropeptides; D011985:Receptors, Serotonin; D018039:Receptors, Tachykinin; D012702:Serotonin Antagonists; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D002211:Capsaicin