Surfactant metabolism in transgenic mice after granulocyte
macrophage-colony stimulating factor ablation.
Ikegami, Machiko, Takashi Ueda, William Hull, Jeffrey A. Whitsett,
Richard C. Mulligan, Glenn Dranoff, Alan H. Jobe.
HARBOR-UCLA MEDICAL CENTER, UCLA SCHOOL OF MEDICINE, TORRANCE, CA
90502, DIVISION OF PULMONARY BIOLOGY, CINCINNATI CHILDREN'S HOSPITAL,
CINCINNATI, OH 45229-2899, WHITEHEAD INSTITUTE FOR BIOMEDICAL
RESEARCH, MASSACHUSETTS INSTITUTE OF TECHNOLOGY, CAMBRIDGE, MA 02142,
DANA-FARBER CANCER INSTITUTE, HARVARD MEDICAL SCHOOL, BOSTON, MA
02115
APStracts 2:0216L, 1995.
Mice made GM-CSF deficient by homologous recombination maintain normal
steady state hematopoiesis but have an alveolar accumulation of
surfactant lipids and protein that is similar to pulmonary alveolar
proteinosis in man. We asked how GM-CSF deficiency alters surfactant
metabolism and function in mice. Alveolar and lung tissue saturated
phosphatidylcholine (Sat PC) were increased 6 to 8 fold in 7-9 wk old
GM-CSF deficient mice relative to controls. Incorporation of
radiolabeled palmitate and choline into Sat PC was higher in GM-CSF
mice than control mice, and no loss of labeled Sat PC occurred from
the lungs of GM-CSF deficient mice. Secretion of radiolabeled Sat PC
to the alveolus was similar in GM-CSF deficient and control mice.
Labeled Sat PC and surfactant protein A (SP-A) given by tracheal
instillation were cleared rapidly in control mice, but there was no
measurable loss from the lungs of GM-CSF deficient mice. The function
of the surfactant from GM-CSF deficient mice was normal when tested
in preterm surfactant deficient rabbits. GM-CSF deficiency results in
a catabolic defect for Sat PC and SP-A.
Received 18 May 1995; accepted in final form 8 November 1995.
APS Manuscript Number L155-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95