title: Phospholipase A2 in experimental allergic bronchitis: a lesson from mouse and rat models.
abstract: BACKGROUND
  Phospholipases A2 (PLA2) hydrolyzes phospholipids, initiating the production of inflammatory lipid mediators. We have previously shown that in rats, sPLA2 and cPLA2 play opposing roles in the pathophysiology of ovalbumin (OVA)-induced experimental allergic bronchitis (OVA-EAB), an asthma model: Upon disease induction sPLA2 expression and production of the broncho-constricting CysLTs are elevated, whereas cPLA2 expression and the broncho-dilating PGE2 production are suppressed. These were reversed upon disease amelioration by treatment with an sPLA2 inhibitor. However, studies in mice reported the involvement of both sPLA2 and cPLA2 in EAB induction.
  
  
  OBJECTIVE
  To examine the relevance of mouse and rat models to understanding asthma pathophysiology.
  
  
  METHODS
  OVA-EAB was induced in mice using the same methodology applied in rats. Disease and biochemical markers in mice were compared with those in rats.
  
  
  RESULTS
  As in rats, EAB in mice was associated with increased mRNA of sPLA2, specifically sPLA2gX, in the lungs, and production of the broncho-constricting eicosanoids CysLTs, PGD2 and TBX2 in bronchoalveolar lavage (BAL). In contrast, EAB in mice was associated also with elevated cPLA2 mRNA and PGE2 production. Yet, treatment with an sPLA2 inhibitor ameliorated the EAB concomitantly with reverting the expression of both cPLA2 and sPLA2, and eicosanoid production.
  
  
  CONCLUSIONS
  In both mice and rats sPLA2 is pivotal in OVA-induced EAB. Yet, amelioration of asthma markers in mouse models, and human tissues, was observed also upon cPLA2 inhibition. It is plausible that airway conditions, involving multiple cell types and organs, require the combined action of more than one, essential, PLA2s.
authors.affiliation: Department of Biochemistry, Hebrew University Medical School, Jerusalem, Israel.
authors.forename: Rufayda
authors.initials: R
authors.lastname: Mruwat
authors.forename: Saul
authors.initials: S
authors.lastname: Yedgar
authors.forename: Iris
authors.initials: I
authors.lastname: Lavon
authors.forename: Amiram
authors.initials: A
authors.lastname: Ariel
authors.forename: Miron
authors.initials: M
authors.lastname: Krimsky
authors.forename: David
authors.initials: D
authors.lastname: Shoseyov
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000276:immunology / Q000378:metabolism; D001119:Arginase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D001991:Bronchitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002688:Chitinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003545:Cysteine / Q000276:immunology / Q000378:metabolism; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D054509:Group X Phospholipases A2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015289:Leukotrienes / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D054510:Phospholipases A2, Cytosolic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D054497:Phospholipases A2, Secretory / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000276:immunology / Q000378:metabolism; D051381:Rats; D018077:Receptors, Leukotriene / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D015289:Leukotrienes; D018077:Receptors, Leukotriene; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C112381:cysteinyl-leukotriene; D010047:Ovalbumin; D001094:Arachidonate 5-Lipoxygenase; D054509:Group X Phospholipases A2; D054510:Phospholipases A2, Cytosolic; D054497:Phospholipases A2, Secretory; D002688:Chitinases; C544448:Arg1 protein, mouse; D001119:Arginase; D015232:Dinoprostone; D003545:Cysteine; C083169:leukotriene D4 receptor; D015230:Prostaglandin D2