GM-CSF gene expression is normal but protein release is absent in a patient with pulmonary alveolar proteinosis.
Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by an excessive accumulation of surfactant lipids and proteins in the alveolar space. In mice with a homozygous deletion of granulocyte macrophage-colony stimulating factor (GM-CSF), their phenotype mimics PAP. To evaluate whether the knockout mouse model mimics human disease, we evaluated GM-CSF expression in alveolar macrophages from a patient with PAP. We performed multiple whole lung lavages on a patient with PAP, and cultured BAL cells in the presence or absence of LPS. In contrast to the GM-CSF knockout mouse, human BAL cells from a patient with PAP expressed mRNA for GM-CSF following LPS stimulation. However, similar to the knockout mouse, GM-CSF protein release from BAL cells was undetectable with or without LPS. BAL cells from normal human controls released GM-CSF in abundance after LPS stimulation. In BAL cells from the patient with PAP, neutralization of interleukin-10 (IL-10) by anti-IL-10 antibody, resulted in enhanced GM-CSF production. Thus, alveolar macrophages from a PAP lung have deficient GM-CSF production analogous to the GM-CSF knockout mice; in contrast, human cells from a PAP lung have an intact GM-CSF gene. This case report illustrates an important difference between the knockout mouse model of PAP and the human disease.
Tchou-Wong
K M
KM
Department of Medicine, Bellevue Chest Service, New York University Medical Center, New York, USA.
Harkin
T J
TJ
Chi
C
C
Bodkin
M
M
Rom
W N
WN
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000378:metabolism; D011649:Pulmonary Alveolar Proteinosis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor