Pleural fluid eosinophils suppress local IgE-mediated protein exudation in rats.
Eosinophils are supposed to play a critical role in the pathology of several allergic diseases because after activation they can release toxic and proinflammatory agents. In this study we have investigated whether IgE-mediated rat pleurisy could be affected by an ongoing pleural eosinophilic inflammatory response. IgE-passively sensitized rats were challenged with an intrapleural (i.pl.) injection of allergen (dinitrophenylated bovine serum albumin, 1 microgram/cavity) and exudation assessed by measuring the amount of protein extravasated into the pleural cavity within 4 h. We have confirmed that lipopolysaccharide (LPS) stimulation (250 ng/cavity i.pl.) was followed by a marked pleural neutrophilia, apparent at 3 h, which was followed by an eosinophil accumulation noted within 48-72 h postchallenge. We have also confirmed that a boiled sample of LPS pleural washing (LPS-PW, 200 microliters i.pl.) caused selective eosinophilia in recipient rats. Pleural exudation remained unaltered when the allergenic challenge was performed 3 h after LPS in a condition of intense pleural fluid neutrophilia. In contrast, this was significantly reduced (P < .001) when the challenge occurred 72 h after LPS or 24 h after LPS-PW in selective pleural fluid eosinophilia. In another series of experiments repeated daily i.pl. injections of platelet-activating factor (PAF; 1 microgram/cavity) resulted in a progressive increase in eosinophil number recovered from the pleural cavity. The values were 1.2 +/- 0.2, 3.0 +/- 0.2, and 5.8 +/- 0.5 x 10(6) eosinophils/cavity (mean +/- SEM) after 0, 1, and 4 injections, respectively. Allergen challenge performed after 0, 1, or 4 PAF stimulations led to pleural protein levels of 88.6 +/- 5.7, 33.7 +/- 0.7, and 19.4 +/- 2.3 mg/cavity, respectively, indicating that the allergic pleurisy is inhibited in a manner dependent on the magnitude of eosinophil accumulation. Furthermore, the impairment of PAF-induced eosinophil accumulation by cetirizine (30 mg/kg i.p.) restored the exudatory response. Exudation triggered by compound 48/80 (25 micrograms/cavity), histamine (200 micrograms/cavity), or 5-hydroxytryptamine (100 micrograms/cavity) was not affected by four previous PAF daily injections. The findings indicate that allergen-induced exudation is selectively down-regulated in the eosinophil-enriched pleural space of rats, a suppression that increased with increasing eosinophil number and disappeared after chemical impairment of the eosinophilia.
Bandeira-Melo
C
C
Departamento de Fisiologia e Farmacodinamica, Oswaldo Cruz Institute, Rio de Janeiro, Brazil.
e Silva
P M
PM
Cordeiro
R S
RS
Martins
M A
MA
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D004140:Dinitrophenols; D004802:Eosinophilia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D004804:Eosinophils / Q000276:immunology / Q000502:physiology*; D005122:Exudates and Transudates / Q000166:cytology*; D005260:Female; D006632:Histamine / Q000633:toxicity; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology; D007073:Immunoglobulin E / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008407:Mast Cells / Q000166:cytology; D010972:Platelet Activating Factor / Q000633:toxicity; D010996:Pleural Effusion / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000633:toxicity; D012710:Serum Albumin, Bovine; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
D001798:Blood Proteins; D004140:Dinitrophenols; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D012701:Serotonin; D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine