國家衛生研究院 NHRI:Item 3990099045/10236

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Title:	Human placenta-derived multipotent cells (PDMCs) protect against Klebsiella pneumoniae-induced pneunomia by enhancing polymorphonuclear granulocytes (PMN) functions
Authors:	Wang, LT;Chao, YY;Lee, W;Huang, LY;Liu, KJ;Siu, LK;Yen, BL
Contributors:	Institute of Cellular and Systems Medicine;Division of Infectious Diseases;National Institute of Cancer Research
Abstract:	Human mesenchymal stem cells (MSCs) are multilineage somatic progenitors with strong immunomodulatory properties which have been well-demonstrated for T lymphocytes and dendritic cells/macrophages. However, interactions with neutrophils (polymorphonuclear granulocytes or PMNs)—the most abundant population of human leukocytes—are less well understood. Therefore, we investigated the interactions of human placenta-derived multipotent cells (PDMCs), a population of fetal-stage MSCs, with PMNs through in vitro studies and a mouse model of Klebsiella pneumoniae (KP)-induced pneumonia. KP is a highly virulent gram-negative bacterium and a leading cause of community- and hospital-acquired infections, especially pneumonia. We found that after co-culture with PDMCs, PMN expression of CD11b—a marker of activation—as well as phagocytosis of FITC- labeled KP was significantly increased. Moreover, PMN oxidative metabolism was significantly increased as well, which manifested as increased anti-bacterial activity and improved killing of KP. To ascertain the therapeutic efficacy of PDMCs on bacterial infections, we infected wild type mice with KP by intratracheal inoculation with subsequent intravenous administration of PDMCs. Surprisingly, while injection of PDMCs reduced the influx of PMNs in KP-infected lung tissue, respiratory burst activity was simultaneously enhanced. PDMC treatment also decreased bacterial counts both locally in lung tissue and systemically in the bloodstream. Most importantly, administration of PDMCs significantly increased survival rates in this mouse model of KP pneumonia. Taken together, we found that PDMCs enhance PMN functions in vitro and in vivo towards KP without increasing overall lung inflammatory damage. Our data strongly implicate a possible therapeutic role for PDMCs towards gram-negative bacterial infections.
Date:	2016-08
Relation:	European Journal of Immunology. 2016 Aug;46(Suppl. 1):1242.
Link to:	http://dx.doi.org/10.1002/eji.201670200
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0014-2980&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000391563600009
Appears in Collections:	[Betty Lin-Ju Yen] Conference Papers/Meeting Abstract [Leung-Kei Siu] Conference Papers/Meeting Abstract [Ko-Jiunn Liu] Conference Papers/Meeting Abstract

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