Secreted phospholipases A2 induce the expression of chemokines in microvascular endothelium.
Acute respiratory distress syndrome (ARDS) is characterized by alterations in microvascular permeability. In ARDS secreted phospholipase A(2) (sPLA(2)) IB and IIA are found to be highly upregulated. In this study, we therefore investigated the influence of exogenously added sPLA(2)-IB and sPLA(2)-IIA on the production of chemokines and adhesion molecules in lung microvascular endothelial cells (LMVEC). Treatment of LMVEC with sPLA(2)s resulted in a significant increase in the production of chemokines and adhesion molecules due to an increased expression of their mRNA and in an enhanced release of oleic acid. The upregulation of chemokines and adhesion molecules by LPS was stronger in the presence of sPLA(2). Activation of NF-kappaB occurred upon stimulation with sPLA(2). Moreover the MAPkinase pERK seems to be involved since a specific pERK inhibitor, e.g., U0126, but not a p38Kinase inhibitor, e.g., SB203580 prevented sPLA(2)-induced chemokine upregulation. Our data therefore suggest that LMVEC are a highly sensitive target for the direct action of extracellular sPLA(2)s.
Beck
Grietje Ch
GCh
Institute of Anaesthesiology and Critical Care Medicine, University of Mannheim, Th-Kutzer Ufer 1-3, 68167 Mannheim, Germany. g.beck@anaes.ma.uni-heidelberg.de
Yard
Benito A
BA
Schulte
Jutta
J
Haak
Markus
M
van Ackern
Klaus
K
van der Woude
Fokko J
FJ
Kaszkin
Marietta
M
D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D054500:Group IB Phospholipases A2; D054501:Group II Phospholipases A2; D019763:Heparin Lyase / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000098:blood supply; D008833:Microcirculation; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism; D010741:Phospholipases A / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D018925:Chemokines; D016328:NF-kappa B; D019301:Oleic Acid; D020928:Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054500:Group IB Phospholipases A2; D054501:Group II Phospholipases A2; C516202:PLA2G1B protein, human; D019763:Heparin Lyase