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Article

Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus Aureus

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
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Author to whom correspondence should be addressed.
Academic Editors: Stephen Y. Chan and Alfonso Eirin
Cells 2021, 10(7), 1731; https://doi.org/10.3390/cells10071731
Received: 15 April 2021 / Revised: 25 June 2021 / Accepted: 3 July 2021 / Published: 8 July 2021
(This article belongs to the Collection The Endothelial Cell in Lung Inflammation)
Lung endothelial dysfunction is a key feature of acute lung injury (ALI) and clinical acute respiratory distress syndrome (ARDS). Previous studies have identified the lipid-generating enzyme, group V phospholipase A2 (gVPLA2), as a mediator of lung endothelial barrier disruption and inflammation. The current study aimed to determine the role of gVPLA2 in mediating lung endothelial responses to methicillin-resistant Staphylococcus aureus (MRSA, USA300 strain), a major cause of ALI/ARDS. In vitro studies assessed the effects of gVPLA2 inhibition on lung endothelial cell (EC) permeability after exposure to heat-killed (HK) MRSA. In vivo studies assessed the effects of intratracheal live or HK-MRSA on multiple indices of ALI in wild-type (WT) and gVPLA2-deficient (KO) mice. In vitro, HK-MRSA increased gVPLA2 expression and permeability in human lung EC. Inhibition of gVPLA2 with either the PLA2 inhibitor, LY311727, or with a specific monoclonal antibody, attenuated the barrier disruption caused by HK-MRSA. LY311727 also reduced HK-MRSA-induced permeability in mouse lung EC isolated from WT but not gVPLA2-KO mice. In vivo, live MRSA caused significantly less ALI in gVPLA2 KO mice compared to WT, findings confirmed by intravital microscopy assessment in HK-MRSA-treated mice. After targeted delivery of gVPLA2 plasmid to lung endothelium using ACE antibody-conjugated liposomes, MRSA-induced ALI was significantly increased in gVPLA2-KO mice, indicating that lung endothelial expression of gVPLA2 is critical in vivo. In summary, these results demonstrate an important role for gVPLA2 in mediating MRSA-induced lung EC permeability and ALI. Thus, gVPLA2 may represent a novel therapeutic target in ALI/ARDS caused by bacterial infection. View Full-Text
Keywords: gVPLA2; sPLA2-V; PLA2G5; secretory phospholipase A2; endothelium; ALI; bacterial infection; intravital microscopy; ARDS; MRSA; USA300 gVPLA2; sPLA2-V; PLA2G5; secretory phospholipase A2; endothelium; ALI; bacterial infection; intravital microscopy; ARDS; MRSA; USA300
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MDPI and ACS Style

Htwe, Y.M.; Wang, H.; Belvitch, P.; Meliton, L.; Bandela, M.; Letsiou, E.; Dudek, S.M. Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus Aureus. Cells 2021, 10, 1731. https://doi.org/10.3390/cells10071731

AMA Style

Htwe YM, Wang H, Belvitch P, Meliton L, Bandela M, Letsiou E, Dudek SM. Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus Aureus. Cells. 2021; 10(7):1731. https://doi.org/10.3390/cells10071731

Chicago/Turabian Style

Htwe, Yu Maw, Huashan Wang, Patrick Belvitch, Lucille Meliton, Mounica Bandela, Eleftheria Letsiou, and Steven M. Dudek. 2021. "Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus Aureus" Cells 10, no. 7: 1731. https://doi.org/10.3390/cells10071731

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