Pulmonary inflammation and edema induced by phospholipase A2: global gene analysis and effects on aquaporins and Na+/K+-ATPase.
Victims of snakebite quickly succumb to severe respiratory failure, which can be fatal if left untreated. One of the most toxic components of snake venom is phospholipase A2 (PLA2; EC 3.1.1.4). PLA2 isolated from the elapid, Naja sputatrix, induced pulmonary inflammation and edema when administered intravenously and intratracheally to rats. Analysis of pulmonary gene expression profiles using oligonucleotide microarrays revealed 60 genes whose expression was altered by at least 3-fold in response to intratracheal instillation of PLA2 for 3 h as compared with controls. In addition to genes encoding cytokines and chemokines responsible for inflammatory processes, the Na+/K+-ATPase gene has been found to be involved in edema formation. Real-time PCR, Western blot, and immunohistochemical analyses confirmed that the expression of AQP1 and AQP5 mRNAs and proteins was decreased. Besides providing an experimental model for studies on the pathophysiology of the lung, this investigation yields a clue to the mechanisms by which endogenous PLA2s could mediate inflammation in conditions such as allergy and rheumatoid arthritis.
Department of Biochemistry, Faculty of Medicine, National University of Singapore, S117597, Singapore.
Charmian D N
CD
Cher
Arunmozhiarasi
A
Armugam
Ramkumar
R
Lachumanan
Marelyn-Wintour
MW
Coghlan
Kandiah
K
Jeyaseelan
D000280:Administration, Inhalation; D000818:Animals; D020346:Aquaporins / Q000235:genetics; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D007275:Injections, Intravenous; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010741:Phospholipases A / Q000633:toxicity*; D054467:Phospholipases A2; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012910:Snake Venoms / Q000633:toxicity; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D014882:Water-Electrolyte Balance / Q000187:drug effects
D020346:Aquaporins; D016207:Cytokines; D007527:Isoenzymes; D012910:Snake Venoms; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D000254:Sodium-Potassium-Exchanging ATPase