Tumor necrosis factor-[alpha] decreases surfactant protein b mrna
in murine lung.
Pryhuber, Gloria S., Cindy Bachurski, Raphael Hirsch, Andrea Bacon,
Jeffrey A. Whitsett.
Division of Pulmonary Biology and Division of Rheumatology,
Children's Hospital Medical Center, Cincinnati, Ohio 45229
APStracts 2:0229L, 1995.
Respiratory failure secondary to acute lung inflammation is associated
with quantitative and qualitative abnormalities of pulmonary
surfactant. The surfactant associated proteins, SP-A, B and C are
critical for normal surfactant function, synthesis and metabolism.
Tumor necrosis factor - alpha (TNF-[alpha]), a primary mediator of
acute lung inflammation, decreased surfactant protein gene expression
in vitro (32, 34). In the present in vivo study, transient T cell
activation and TNF-[alpha] release was initiated by intraperitoneal
administration of anti-CD3 antibody, 145-2C11. Serum TNF-[alpha] was
elevated two hours after injection of the antibody. SP-B and SP-C
mRNA were decreased 12 and 24 hours after antibody treatment.
Intratracheal (IT) murine TNF-[alpha] also resulted in decreased SP-B
and SP-C mRNA levels in the bronchiolar and alveolar epithelium of
adult FVB/N mice, as demonstrated by S1 nuclease protection and in
situ hybridization assays, despite minimal histologic inflammation.
SP-A mRNA was not significantly altered following anti-CD3 antibody
and was only mildly decreased following TNF-[alpha]. As previously
reported, ICAM-1 mRNA was elevated following IT TNF-[alpha].
Surfactant protein insufficiency contributes to the pathogenesis of
pulmonary diseases associated with increased TNF-a, such as ARDS and
pneumonia (8). TNF-[alpha] mediated decrease in surfactant protein
gene expression may contribute to the surfactant dysfunction and
atelectasis observed in inflammatory lung diseases.
Received 10 August 1995; accepted in final form 28 November 1995.
APS Manuscript Number L253-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95