PMID- 29806827
OWN - NLM
STAT- MEDLINE
DCOM- 20180806
LR  - 20181202
IS  - 1940-087X (Electronic)
IS  - 1940-087X (Linking)
IP  - 135
DP  - 2018 May 9
TI  - Assessment of the Cytotoxic and Immunomodulatory Effects of Substances in Human 
      Precision-cut Lung Slices.
LID - 10.3791/57042 [doi]
LID - 57042
AB  - Respiratory diseases in their broad diversity need appropriate model systems to 
      understand the underlying mechanisms and enable development of new therapeutics. 
      Additionally, registration of new substances requires appropriate risk assessment 
      with adequate testing systems to avoid the risk of individuals being harmed, for 
      example, in the working environment. Such risk assessments are usually conducted 
      in animal studies. In view of the 3Rs principle and public skepticism against 
      animal experiments, human alternative methods, such as precision-cut lung slices 
      (PCLS), have been evolving. The present paper describes the ex vivo technique of 
      human PCLS to study the immunomodulatory potential of low-molecular-weight 
      substances, such as ammonium hexachloroplatinate (HClPt). Measured endpoints 
      include viability and local respiratory inflammation, marked by altered secretion 
      of cytokines and chemokines. Pro-inflammatory cytokines, tumor necrosis factor 
      alpha (TNF-alpha), and interleukin 1 alpha (IL-1alpha) were significantly increased in 
      human PCLS after exposure to a sub-toxic concentration of HClPt. Even though the 
      technique of PCLS has been substantially optimized over the past decades, its 
      applicability for the testing of immunomodulation is still in development. 
      Therefore, the results presented here are preliminary, even though they show the 
      potential of human PCLS as a valuable tool in respiratory research.
FAU - Neuhaus, Vanessa
AU  - Neuhaus V
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), German 
      Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive 
      Lung Disease Hannover (BREATH), Member of REBIRTH Cluster of Excellence.
FAU - Danov, Olga
AU  - Danov O
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), German 
      Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive 
      Lung Disease Hannover (BREATH), Member of REBIRTH Cluster of Excellence.
FAU - Konzok, Sebastian
AU  - Konzok S
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), German 
      Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive 
      Lung Disease Hannover (BREATH), Member of REBIRTH Cluster of Excellence.
FAU - Obernolte, Helena
AU  - Obernolte H
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), German 
      Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive 
      Lung Disease Hannover (BREATH), Member of REBIRTH Cluster of Excellence.
FAU - Dehmel, Susann
AU  - Dehmel S
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), German 
      Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive 
      Lung Disease Hannover (BREATH), Member of REBIRTH Cluster of Excellence.
FAU - Braubach, Peter
AU  - Braubach P
AD  - Institute for Pathology, Hannover Medical School, German Center for Lung Research 
      (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover 
      (BREATH).
FAU - Jonigk, Danny
AU  - Jonigk D
AD  - Institute for Pathology, Hannover Medical School, German Center for Lung Research 
      (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover 
      (BREATH).
FAU - Fieguth, Hans-Gerd
AU  - Fieguth HG
AD  - Division of Thoracic and Vascular Surgery, Klinikum Region Hannover (KRH).
FAU - Zardo, Patrick
AU  - Zardo P
AD  - Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), 
      Hannover Medical School, German Center for Lung Research (DZL), Biomedical 
      Research in Endstage and Obstructive Lung Disease Hannover (BREATH).
FAU - Warnecke, Gregor
AU  - Warnecke G
AD  - Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG), 
      Hannover Medical School, German Center for Lung Research (DZL), Biomedical 
      Research in Endstage and Obstructive Lung Disease Hannover (BREATH).
FAU - Martin, Christian
AU  - Martin C
AD  - Institute of Pharmacology and Toxicology, RWTH Aachen University.
FAU - Braun, Armin
AU  - Braun A
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), German 
      Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive 
      Lung Disease Hannover (BREATH), Member of REBIRTH Cluster of Excellence; 
      Institute for Immunology, Hannover Medical School.
FAU - Sewald, Katherina
AU  - Sewald K
AD  - Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), German 
      Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive 
      Lung Disease Hannover (BREATH), Member of REBIRTH Cluster of Excellence; 
      katherina.sewald@item.fraunhofer.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Video-Audio Media
DEP - 20180509
PL  - United States
TA  - J Vis Exp
JT  - Journal of visualized experiments : JoVE
JID - 101313252
SB  - IM
MH  - Animals
MH  - Cytotoxicity Tests, Immunologic/*methods
MH  - Humans
MH  - Immunomodulation/*immunology
MH  - Lung/*pathology
MH  - Microscopy, Confocal/*methods
PMC - PMC6101160
EDAT- 2018/05/29 06:00
MHDA- 2018/08/07 06:00
PMCR- 2018/05/09
CRDT- 2018/05/29 06:00
PHST- 2018/05/29 06:00 [entrez]
PHST- 2018/05/29 06:00 [pubmed]
PHST- 2018/08/07 06:00 [medline]
PHST- 2018/05/09 00:00 [pmc-release]
AID - 57042 [pii]
AID - 10.3791/57042 [doi]
PST - epublish
SO  - J Vis Exp. 2018 May 9;(135):57042. doi: 10.3791/57042.