Role of inducible nitric oxide synthase expressed by alveolar macrophages in high mobility group box 1--induced acute lung injury.
OBJECTIVE
The role of inducible nitric oxide synthase (iNOS) expressed by alveolar macrophages in acute lung injury induced by high mobility group box 1 (HMGB1) was explored.


METHODS
Primary rat alveolar macrophages (PRAMs) were stimulated with HMGB1 to analyze iNOS expression. Alveolar macrophages and iNOS were inhibited by gadolinium chloride and 1400W in rats challenged by HMGB1 intratracheally.


METHODS
Western Blot was applied to assay iNOS expression in PRAMs. Indices for acute lung injury in rats were measured. Immunocytochemistry was used to localize iNOS in squarebronchoalveolar lavage (BAL) cells. The enzyme activities of iNOS and constitutive nitric oxide synthase (cNOS) for BAL cells were determined.


RESULTS
A time- and concentration-dependent response of iNOS expression in PRAMs to HMGB1 induction was observed. Intratracheal instillation of HMGB1 produced persistently exacerbated acute lung inflammation, induction of iNOS in alveolar macrophages and increased lung nitric oxide production in rats. Abrogation of iNOS or macrophages attenuated lung inflammation, nitric oxide in BAL fluid, and iNOS activity of BAL cells, but had no significant effect on cNOS activity of BAL cells in rats challenged by HMGB1.


CONCLUSIONS
Inducible nitric oxide synthase expressed by alveolar macrophages facilitates the development of HMGB1-induced acute lung injury.
Ren
D
D
Department of Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing, 100005, People's Republic of China. dbren-7194@163.com
Sun
R
R
Wang
S
S
D000418:Albumins / Q000032:analysis; D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D024243:HMGB1 Protein / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D000418:Albumins; D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; D024243:HMGB1 Protein; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009573:Nitrites; D011994:Recombinant Proteins; D005682:Gadolinium; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; C038958:gadolinium chloride