title: Acute pulmonary inflammation induced by exposure of the airways to staphylococcal enterotoxin type B in rats.
abstract: Staphylococcus aureus is a gram-positive bacterium that produces several enterotoxins, which are responsible for most part of pathological conditions associated to staphylococcal infections, including lung inflammation. This study aimed to investigate the underlying inflammatory mechanisms involved in leukocyte recruitment in rats exposed to staphylococcal enterotoxin B (SEB). Rats were anesthetized with pentobarbital sodium and intratracheally injected with either SEB or sterile phosphate-buffered saline (PBS, 0.4 ml). Airways exposition to SEB (7.5-250 ng/trachea) caused a dose- and time-dependent neutrophil accumulation in BAL fluid, the maximal effects of which were observed at 4 h post-SEB exposure (250 ng/trachea). Eosinophils were virtually absent in BAL fluid, whereas mononuclear cell counts increased only at 24 h post-SEB. Significant elevations of granulocytes in bone marrow (mature and immature forms) and peripheral blood have also been detected. In BAL fluid, marked elevations in the levels of lipid mediators (LTB(4) and PGE(2)) and cytokines (TNF-alpha, IL-6 and IL-10) were observed after SEB instillation. The SEB-induced neutrophil accumulation in BAL fluid was reduced by pretreatment with dexamethasone (0.5 mg/kg), the COX-2 inhibitor celecoxib (3 mg/kg), the selective iNOS inhibitor compound 1400 W (5 mg/kg) and the lipoxygenase inhibitor AA-861 (200 microg/kg). In separate experiments carried out with rat isolated peripheral neutrophils, SEB failed to induce neutrophil adhesion to serum-coated plates and chemotaxis. In conclusion, rat airways exposition to SEB causes a neutrophil-dependent lung inflammation at 4 h as result of the release of proinflammatory (NO, PGE(2), LTB(4), TNF-alpha, IL-6) and anti-inflammatory mediators (IL-10).
authors.affiliation: Department of Pharmacology, State University of Campinas, P.O. Box 6111, 13084-971, Campinas, SP, Brazil. ivanidesouza@fcm.unicamp.br <ivanidesouza@fcm.unicamp.br>
authors.forename: Ivani A
authors.initials: IA
authors.lastname: Desouza
authors.forename: Carla F
authors.initials: CF
authors.lastname: Franco-Penteado
authors.forename: Enilton A
authors.initials: EA
authors.lastname: Camargo
authors.forename: Carmen S P
authors.initials: CS
authors.lastname: Lima
authors.forename: Simone A
authors.initials: SA
authors.lastname: Teixeira
authors.forename: Marcelo N
authors.initials: MN
authors.lastname: Muscará
authors.forename: Gilberto
authors.initials: G
authors.lastname: De Nucci
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D001853:Bone Marrow / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D000068579:Celecoxib; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology*; D007442:Intubation, Intratracheal; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011023:Pneumonia, Staphylococcal / Q000097:blood / Q000276:immunology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D016227:Benzoquinones; D016207:Cytokines; D004768:Enterotoxins; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D007975:Leukotriene B4; C031818:enterotoxin B, staphylococcal; D003907:Dexamethasone; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D000068579:Celecoxib; D015232:Dinoprostone