Abstract |
Inflammatory mediators are released from injured tissues being responsible for the first steps of inflammatory processes. Multidrug efflux transporters, members of the ATP-binding cassette (ABC) family, are ubiquitously expressed. ABCC molecules transport several endogenous substances, including leukotriene C4 ( LTC4) and PGE2, which are involved in zymosan-induced inflammation. The present study investigated the role played by ABCC transporters on zymosan-induced peritonitis in mice. Most of the resident peritoneal cells were macrophages, based on their morphology and membrane-activated complex 3 expression. RT-PCR demonstrated that these cells expressed ABCC, and ABCC activity was analyzed in vivo via the s.c. injection of ABCC inhibitors [ probenecid (PROB) 200 mg/kg or MK571 20 mg/kg], followed by an i.v. injection of carboxyfluorescein diacetate (CFDA), an ABCC fluorescent substrate. Both inhibitors increased CFDA accumulation, suggesting ABCC impairment. Moreover, ABCC reversors decreased zymosan-induced plasma exudation by 86.6 +/- 7.4 and 97.6 +/- 2.3%, a feature related to a diminished secretion of LTC(4) (65.1+/-11 and 47.8+/-9.9%) and PGE(2) (under basal levels). Cell migration was inhibited similarly. Furthermore, PROB and MK571 inhibited IL-1ss by 83.4 +/- 13 and 71.2 +/- 13.4% and TNF-alpha content by 47 +/- 4.5 and 28.9 +/- 0.8%, respectively. NO metabolites and reactive oxygen species production were also reduced. The present results suggest that ABCC molecules have a relevant role in the acute inflammatory response produced by zymosan in mice.
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Authors | Daniela F P Leite, Juliana Echevarria-Lima, Samira Cardoso Ferreira, João B Calixto, Vivian M Rumjanek |
Journal | Journal of leukocyte biology
(J Leukoc Biol)
Vol. 82
Issue 3
Pg. 630-7
(Sep 2007)
ISSN: 0741-5400 [Print] United States |
PMID | 17576824
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Differentiation
- Bronchodilator Agents
- Eicosanoids
- Interleukin-1beta
- Lipopolysaccharides
- Multidrug Resistance-Associated Proteins
- Propionates
- Quinolines
- Tumor Necrosis Factor-alpha
- monocyte-macrophage differentiation antigen
- verlukast
- Zymosan
- multidrug resistance-associated protein 1
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Topics |
- Animals
- Antigens, Differentiation
(metabolism)
- Bronchodilator Agents
(pharmacology)
- Cell Movement
- Chemotaxis, Leukocyte
- Edema
(prevention & control)
- Eicosanoids
(antagonists & inhibitors, metabolism)
- Inflammation
- Interleukin-1beta
(metabolism)
- Lipopolysaccharides
(pharmacology)
- Luminescence
- Macrophage Activation
- Macrophages, Peritoneal
(cytology, drug effects, metabolism)
- Male
- Mice
- Monocytes
(cytology, metabolism)
- Multidrug Resistance-Associated Proteins
(antagonists & inhibitors, genetics, metabolism)
- Peritonitis
(chemically induced, prevention & control)
- Propionates
(pharmacology)
- Quinolines
(pharmacology)
- Respiratory Burst
- Tumor Necrosis Factor-alpha
(metabolism)
- Zymosan
(toxicity)
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