Am. J. Respir. Crit. Care Med., Volume 156, Number 6, December 1997, 1999-2002

GM-CSF Gene Expression Is Normal but Protein Release Is Absent in a Patient with Pulmonary Alveolar Proteinosis

KAM-MENG TCHOU-WONG, TIMOTHY J. HARKIN, CHUANXIANG CHI, MARION BODKIN, and WILLIAM N. ROM

Division of Pulmonary and Critical Care Medicine, Departments of Medicine, Bellevue Chest Service, Environmental Medicine, and Microbiology, New York University Medical Center, New York, New York

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, Harkin TJ, Chi C, Bodkin M, Rom WN. GM-CSF gene expression is normal but protein release is absent in a patient with pulmonary alveolar proteinosis.

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