Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.2.1.7 (
BAL
)
1,977
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Acute pulmonary inflammation is still a frightening complication in intensive care units. In our previous study, we determined that
heme oxygenase
(HO)-1 had anti-inflammatory effects in pulmonary inflammation. Recent literature has emphasized a link between HO-1 and the nucleotide adenosine. Since adenosine A
2A
- and A
2B
-receptors play a pivotal role in pulmonary inflammation, we investigated their link to the enzyme HO-1. In a murine model of pulmonary inflammation, the activation of HO-1 by hemin significantly decreased polymorphonuclear leukocyte (PMN) migration into the lung. This anti-inflammatory reduction of PMN migration was abolished in A
2A
- and A
2B
-knockout mice. Administration of hemin significantly reduced chemokine levels in the
BAL
of wild-type animals but had no effects in A
2A
-/-
and A
2B
-/-
mice. Microvascular permeability was significantly attenuated in HO-1-stimulated wild-type mice, but not in A
2A
-/-
and A
2B
-/-
mice. The activity of HO-1 rose after LPS inhalation in wild-type animals and, surprisingly, also in A
2A
-/-
and A
2B
-/-
mice after the additional administration of hemin. Immunofluorescence images of animals revealed alveolar macrophages to be the major source of HO-1 activity in both knockout strains-in contrast to wild-type animals, where HO-1 was also significantly augmented in the lung tissue.
In vitro
studies on PMN migration further confirmed our
in vivo
findings. In conclusion, we linked the anti-inflammatory effects of HO-1 to functional A
2A
/A
2B
-receptor signaling under conditions of pulmonary inflammation. Our findings may explain why targeting HO-1 in acute pulmonary inflammation has failed to prove effective in some patients, since septic patients have altered adenosine receptor expression.
...
PMID:Anti-inflammatory Effects of Heme Oxygenase-1 Depend on Adenosine A
2A
- and A
2B
-Receptor Signaling in Acute Pulmonary Inflammation. 2932 25
