國家衛生研究院 NHRI:Item 3990099045/12041

NHRI > National Institute of Infectious Diseases and Vaccinology > Huey-Kang Sytwu > Periodical Articles > Item 3990099045/12041

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Title:	Staphylococcal phosphatidylinositol-specific phospholipase C potentiates lung injury via complement sensitisation
Authors:	Lin, YC;Liao, YJ;Lee, YH;Tseng, SF;Liu, JY;Chen, YS;Shui, HA;Lin, FZ;Lin, KH;Chen, YC;Tsai, MC;Sytwu, HK;Wang, CC;Chuang, YP
Contributors:	National Institute of Infectious Diseases and Vaccinology
Abstract:	Staphylococcus aureus is frequently isolated from patients with community-acquired pneumonia and acute respiratory distress syndrome (ARDS). ARDS is associated with staphylococcal phosphatidylinositol-specific phospholipase C (PI-PLC); however, the role of PI-PLC in the pathogenesis and progression of ARDS remains unknown. Here, we showed that recombinant staphylococcal PI-PLC possesses enzyme activity that causes shedding of glycosylphosphatidylinositol-anchored CD55 and CD59 from human umbilical vein endothelial cell surfaces and triggers cell lysis via complement activity. Intranasal infection with PI-PLC-positive S. aureus resulted in greater neutrophil infiltration and increased pulmonary oedema compared with a plc-isogenic mutant. Although indistinguishable proinflammatory genes were induced, the wild-type strain activated higher levels of C5a in lung tissue accompanied by elevated albumin instillation and increased lactate dehydrogenase release in bronchoalveolar lavage fluid compared with the plc(-) mutant. Following treatment with cobra venom factor to deplete complement, the wild-type strain with PI-PLC showed a reduced ability to trigger pulmonary permeability and tissue damage. PI-PLC-positive S. aureus induced the formation of membrane attack complex, mainly on type II pneumocytes, and reduced the level of CD55/CD59, indicating the importance of complement regulation in pulmonary injury. In conclusion, S. aureus PI-PLC sensitised tissue to complement activation leading to more severe tissue damage, increased pulmonary oedema, and ARDS progression.
Date:	2019-07
Relation:	Cellular Microbiology. 2019 Jul:Article number e13085.
Link to:	http://dx.doi.org/10.1111/cmi.13085
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1462-5814&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000476180200001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85069915937
Appears in Collections:	[Huey-Kang Sytwu] Periodical Articles

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