PMID- 10022268
OWN - NLM
STAT- MEDLINE
DCOM- 19990225
LR  - 20190819
IS  - 0378-4274 (Print)
IS  - 0378-4274 (Linking)
VI  - 102-103
DP  - 1998 Dec 28
TI  - Role of inflammatory cytokines and nitric oxide in hepatic and pulmonary 
      toxicity.
PG  - 289-93
AB  - Exposure of humans and experimental animals to inhaled irritants such as ozone, 
      induces an acute inflammatory response and lung injury. We hypothesize that 
      macrophage-derived inflammatory cytokines and cytotoxic mediators contribute to 
      the pathogenic process. Treatment of rats with ozone (2 ppm, 3 h) results in 
      damage to the alveolar epithelium and increased protein in lung lavage fluid. 
      This is associated with an increase in the number of macrophages in the lung. We 
      found that these cells are activated to release the proinflammatory cytokine 
      tumor necrosis factor-alpha (TNF alpha) which has been implicated in tissue 
      injury. Following ozone inhalation, alveolar macrophages also produce increased 
      amounts of the cytotoxic mediator, nitric oxide. This response is time-dependent 
      and correlated with expression of inducible nitric oxide synthase (NOS II) 
      protein and mRNA. Inhibition of macrophages with gadolinium chloride abrogates 
      ozone-induced inflammation, mediator production and tissue injury. These data 
      demonstrate, that macrophages and mediators they release contribute to 
      irritant-induced lung injury. Ozone inhalation also caused alterations in the 
      liver, including increased nitric oxide production and protein synthesis 
      suggesting that ozone induces an acute phase response. We speculate that this is 
      mediated by cytokines such as TNF alpha produced by alveolar macrophages. In this 
      regard we noted increased expression of TNF alpha in both lung and liver tissue. 
      Thus cytokines produced locally by macrophages following toxicant exposure may 
      exert pathophysiologic effects outside the target organ.
FAU - Laskin, D L
AU  - Laskin DL
AD  - Environmental and Occupational Health Sciences Institute, Rutgers University and 
      University of Medicine and Dentistry, New Jersey-Robert Wood Johnson Medical 
      School, Piscataway 08854-8020, USA.
FAU - Heck, D E
AU  - Heck DE
FAU - Laskin, J D
AU  - Laskin JD
LA  - eng
GR  - ES04738/ES/NIEHS NIH HHS/United States
GR  - ES06897/ES/NIEHS NIH HHS/United States
GR  - GM34310/GM/NIGMS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 66H7ZZK23N (Ozone)
SB  - IM
MH  - Animals
MH  - Female
MH  - Liver/*drug effects
MH  - Lung/*drug effects
MH  - Nitric Oxide/*physiology
MH  - Ozone/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - S0378-4274(98)00316-6 [pii]
AID - 10.1016/s0378-4274(98)00316-6 [doi]
PST - ppublish
SO  - Toxicol Lett. 1998 Dec 28;102-103:289-93. doi: 10.1016/s0378-4274(98)00316-6.