Pleural mesothelial cells express both BLT2 and PPARalpha and mount an integrated response to pleural leukotriene B4.
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.
Pace
Elisabetta
E
Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Università degli Studi di Palermo, Palermo, Italy. pace@ibim.cnr.it
Ferraro
Maria
M
Mody
Christopher H
CH
Melis
Mario R
MR
Scafidi
Valeria
V
Bonanno
Anna
A
Profita
Mirella
M
Giarratano
Antonino
A
Gjomarkaj
Mark
M
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*
C485878:LTB4R2 protein, human; D047493:PPAR alpha; D018102:Receptors, Leukotriene B4; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4