PMID- 18504053
OWN - NLM
STAT- MEDLINE
DCOM- 20080919
LR  - 20181211
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 231
IP  - 1
DP  - 2008 Aug 15
TI  - Ex vivo testing of immune responses in precision-cut lung slices.
PG  - 68-76
LID - 10.1016/j.taap.2008.04.003 [doi]
AB  - The aim of this study was the establishment of precision-cut lung slices (PCLS) 
      as a suitable ex vivo alternative approach to animal experiments for 
      investigation of immunomodulatory effects. For this purpose we characterized the 
      changes of cytokine production and the expression of cell surface markers after 
      incubation of PCLS with immunoactive substances lipopolysaccharide (LPS), 
      macrophage-activating lipopeptide-2 (MALP-2), interferon gamma (IFNgamma), and 
      dexamethasone. Viability of PCLS from wild-type and CD11c-enhanced yellow 
      fluorescent protein (CD11-EYFP)-transgenic mice was controlled by measurement of 
      lactate dehydrogenase (LDH) enzyme activity and live/dead fluorescence staining 
      using confocal microscopy. Cytokines and chemokines were detected with Luminex 
      technology and ELISA. Antigen presenting cell (APC) markers were investigated in 
      living mouse PCLS in situ using confocal microscopy. LPS triggered profound 
      pro-inflammatory effects in PCLS. Dexamethasone prevented LPS-induced production 
      of cytokines/chemokines such as interleukin (IL)-5, IL-1alpha, TNFalpha, 
      IL-12(p40), and RANTES in PCLS. Surface expression of MHC class II, CD40, and 
      CD11c, but not CD86 was present in APCs of naive PCLS. Incubation with LPS 
      enhanced specifically the expression of MHC class II on diverse cells. MALP-2 
      only failed to alter cytokine or chemokine levels, but was highly effective in 
      combination with IFNgamma resulting in increased levels of TNFalpha, IL-12(p40), 
      RANTES, and IL-1alpha. PCLS showed characteristic responses to typical 
      pro-inflammatory stimuli and may thus provide a suitable ex vivo technique to 
      predict the immunomodulatory potency of inhaled substances.
FAU - Henjakovic, M
AU  - Henjakovic M
AD  - Fraunhofer Institute of Toxicology and Experimental Medicine, Department of 
      Immunology, Allergology and Immunotoxicology, Nikolai-Fuchs-Str. 1, 30625 
      Hannover, Germany.
FAU - Sewald, K
AU  - Sewald K
FAU - Switalla, S
AU  - Switalla S
FAU - Kaiser, D
AU  - Kaiser D
FAU - Muller, M
AU  - Muller M
FAU - Veres, T Z
AU  - Veres TZ
FAU - Martin, C
AU  - Martin C
FAU - Uhlig, S
AU  - Uhlig S
FAU - Krug, N
AU  - Krug N
FAU - Braun, A
AU  - Braun A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080411
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Fluoresceins)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Lipopeptides)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Oligopeptides)
RN  - 148504-34-1 (calcein AM)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 82115-62-6 (Interferon-gamma)
RN  - DZX5IUA94D (macrophage stimulatory lipopeptide 2)
RN  - EN464416SI (Ethidium)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Cell Survival
MH  - Chemokines/biosynthesis
MH  - Cytokines/biosynthesis
MH  - Dexamethasone/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Ethidium
MH  - Female
MH  - Fluoresceins
MH  - Fluorescent Dyes
MH  - Image Processing, Computer-Assisted
MH  - Immunity/*physiology
MH  - Interferon-gamma/pharmacology
MH  - Lipopeptides
MH  - Lipopolysaccharides/pharmacology
MH  - Lung/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Oligopeptides/pharmacology
MH  - Tissue Culture Techniques
EDAT- 2008/05/28 09:00
MHDA- 2008/09/20 09:00
CRDT- 2008/05/28 09:00
PHST- 2008/02/06 00:00 [received]
PHST- 2008/04/02 00:00 [revised]
PHST- 2008/04/02 00:00 [accepted]
PHST- 2008/05/28 09:00 [pubmed]
PHST- 2008/09/20 09:00 [medline]
PHST- 2008/05/28 09:00 [entrez]
AID - S0041-008X(08)00160-9 [pii]
AID - 10.1016/j.taap.2008.04.003 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2008 Aug 15;231(1):68-76. doi: 
      10.1016/j.taap.2008.04.003. Epub 2008 Apr 11.