Cyclooxygenase-2-derived prostaglandin E2 and lipoxin A4 accelerate resolution of allergic edema in Angiostrongylus costaricensis-infected rats: relationship with concurrent eosinophilia.
In noninfected rats, challenge with allergen following local IgE sensitization induced a pleurisy marked by intense protein exudation that plateaued from 30 min to 4 h after challenge, reducing thereafter. Infection of rats with Angiostrongylus costaricensis induced a 5-fold increase in blood eosinophil numbers by 25 days postinfection, whereas the numbers of eosinophils in the pleural cavity ranged from normal to a weak increase. In infected rats, identically sensitized, challenge with Ag induced a much shorter duration of pleural edema with complete resolution by 4 h, but no change in the early edema response. In parallel, infection increased the number of eosinophils recovered from the pleural cavity at 4 h, but not at 30 min, following allergen challenge. Pretreatment with IL-5 (100 IU/kg, i.v.) also increased eosinophil numbers in blood and, after allergen challenge, shortened the duration of the pleural edema and increased pleural eosinophil numbers. There were increases in the levels of both PGE2 and lipoxin A4 (LXA4) in pleural exudate. Selective cyclooxygenase (COX)-2 inhibitors, NS-398, meloxicam, and SC-236, did not alter pleural eosinophilia, but reversed the curtailment of the edema in either infected or IL-5-pretreated rats. Pretreatment of noninfected animals with the PGE analogue, misoprostol, or two stable LXA4 analogues did not alter the magnitude of pleural exudation response, but clearly shortened its duration. These results indicate that the early resolution of allergic pleural edema observed during A. costaricensis infection coincided with a selective local eosinophilia and seemed to be mediated by COX-2-derived PGE2 and LXA4.
Bandeira-Melo
C
C
Laboratory of Inflammation, Institute Oswaldo Cruz, Fiocruz, Brazil.
Serra
M F
MF
Diaz
B L
BL
Cordeiro
R S
RS
Silva
P M
PM
Lenzi
H L
HL
Bakhle
Y S
YS
Serhan
C N
CN
Martins
M A
MA
D000284:Administration, Oral; D000801:Angiostrongylus / Q000276:immunology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology; D000947:Antigens, Helminth / Q000008:administration & dosage; D003345:Corticosterone / Q000097:blood; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology*; D004487:Edema / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004802:Eosinophilia / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D005122:Exudates and Transudates / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000502:physiology*; D006967:Hypersensitivity / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D015848:Interleukin-5 / Q000008:administration & dosage; D007527:Isoenzymes / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D017997:Leukotriene C4 / Q000378:metabolism; D044045:Lipoxins; D008297:Male; D016595:Misoprostol / Q000008:administration & dosage; D010996:Pleural Effusion / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010998:Pleurisy / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017206:Strongylida Infections / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000947:Antigens, Helminth; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D015848:Interleukin-5; D007527:Isoenzymes; D044045:Lipoxins; C040527:lipoxin A4; D016595:Misoprostol; D017997:Leukotriene C4; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D003345:Corticosterone