title: Pleural mesothelial cells express both BLT2 and PPARalpha and mount an integrated response to pleural leukotriene B4.
abstract: Leukotriene B(4) (LTB(4)) plays a crucial role in the recruitment of neutrophils into the pleural space. We identified for the first time the mechanisms by which LTB(4) interacts with mesothelial cells and recruits neutrophils in the pleural compartment. Primary pleural mesothelial cells express both the proinflammatory receptor for LTB(4) BLT2, and the anti-inflammatory receptor for LTB(4), PPARalpha. Parapneumonic pleural effusions highly increase BLT2 expression and, via BLT2 activation, increase the adhesion between mesothelial cells and neutrophils and the expression of ICAM-1 on mesothelial cells. The block of PPARalpha further increases both cell adhesion and ICAM-1 expression. BLT2 activation promotes the activation, on mesothelial cells, of STAT-1 but not the activation of NF-kappaB transcription factor. The increase of ICAM-1 expression is achieved via increased tyrosine phosphorylation activity since herbimycin, a tyrosine kinase inhibitor, reduces and since Na orthovanadate, a tyrosine phosphatase inhibitor, further increases ICAM-1 expression. This study demonstrates that pleural mesothelial cells, expressing both proinflammatory and anti-inflammatory LTB(4) receptors, are able to mount an integrated response to LTB(4) with a prevalence of BLT2 activities in the presence of an inflammatory milieu within the pleura.
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Università degli Studi di Palermo, Palermo, Italy. pace@ibim.cnr.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Mody
authors.forename: Mario R
authors.initials: MR
authors.lastname: Melis
authors.forename: Valeria
authors.initials: V
authors.lastname: Scafidi
authors.forename: Anna
authors.initials: A
authors.lastname: Bonanno
authors.forename: Mirella
authors.initials: M
authors.lastname: Profita
authors.forename: Antonino
authors.initials: A
authors.lastname: Giarratano
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004848:Epithelium; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D020556:Neutrophil Infiltration / Q000276:immunology*; D047493:PPAR alpha / Q000096:biosynthesis*; D010994:Pleura / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D010996:Pleural Effusion / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology; D018102:Receptors, Leukotriene B4 / Q000096:biosynthesis*
chemical_list: C485878:LTB4R2 protein, human; D047493:PPAR alpha; D018102:Receptors, Leukotriene B4; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4