title: Bradykinin down-regulates LPS-induced eosinophil accumulation in the pleural cavity of mice through type 2-kinin receptor activation: a role for prostaglandins.
abstract: 1. The role of both exogenously administered and endogenously generated bradykinin (BK) on LPS-induced eosinophil accumulation in the mice pleural cavity was investigated by means of treatment with BK selective receptor agonists/antagonists and captopril. 2. Intrathoracic (i.t.) injection of LPS (250 ng cavity(-1)) induced eosinophil influx at 24 h as previously described (Bozza et al., 1993). Pretreatment with the B1 receptor antagonist des-Arg9-[leu-8]BK (0.025 and 0.25 nmol cavity(-1)) showed no effect on this phenomenon, whereas pretreatment with the B2 receptor antagonists, NPC 17731 (0.025 and 0.25 nmol cavity(-1)) or HOE 140 (2.5 nmol cavity(-1)), increased LPS-induced eosinophil influx. Accordingly, pretreatment with captopril at 10 mg kg(-1) i.p., inhibited eosinophil infiltration induced by LPS in the pleural cavity, suggesting that endogenous BK is down-regulating LPS-induced eosinophil accumulation. 3. BK administered at 15 and 25 nmol cavity(-1), i.t. or i.p. also inhibited LPS-induced eosinophil accumulation. BK alone had no effect on the basal number of leucocytes in the pleural or peritoneal cavity in doses up to 25 nmol cavity(-1). Nevertheless, when injected at doses of 50 and 100 nmol cavity(-1) BK induced leucocyte influx characterized by neutrophil and eosinophil accumulation at 24 h. 4. Similarly to what was observed with BK, a specific B2 receptor agonist, Tyr8BK, administered at 0.25 nmol cavity(-1) i.p., significantly inhibited the eosinophil influx induced by LPS. 5. The mechanism by which B2 receptor agonists inhibit LPS-induced eosinophil accumulation was investigated by pretreating the animals with indomethacin or a selective cyclooxygenase-2 inhibitor, NS-398. Pretreatment with either indomethacin or NS-398 had no effect on eosinophil influx induced by LPS alone, but those drugs were able to restore the LPS-induced eosinophil influx in Tyr8BK (0.25 nmol cavity(-1)) injected mice. 6. In conclusion, endogenously generated bradykinin seems to modulate, through activation of B2 receptors, eosinphil accumulation induced by LPS via a mechanism dependent on prostanoid synthesis.
authors.affiliation: Departamento de Fisiologia e Farmacodinâmica, IOC, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: A R
authors.initials: AR
authors.lastname: Silva
authors.forename: A P
authors.initials: AP
authors.lastname: Larangeira
authors.forename: P
authors.initials: P
authors.lastname: Pacheco
authors.forename: J B
authors.initials: JB
authors.lastname: Calixto
authors.forename: M G
authors.initials: MG
authors.lastname: Henriques
authors.forename: P T
authors.initials: PT
authors.lastname: Bozza
authors.forename: H C
authors.initials: HC
authors.lastname: Castro-Faria-Neto
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D004768:Enterotoxins / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects*; D029968:Escherichia coli Proteins; D005260:Female; D007278:Injections, Spinal; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010538:Peritonitis / Q000139:chemically induced / Q000473:pathology; D010994:Pleura / Q000166:cytology* / Q000187:drug effects; D010998:Pleurisy / Q000139:chemically induced / Q000473:pathology; D011453:Prostaglandins / Q000502:physiology*; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists* / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; D011453:Prostaglandins; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C034151:heat stable toxin (E coli); D002216:Captopril; D001920:Bradykinin