PULMONARY ALVEOLAR PROTEINOSIS - A SPONTANEOUS AND INDUCIBLE DISEASE IN IMMUNODEFICIENT GERM-FREE MICE

Spontaneous pulmonary alveolar proteinosis (PAP), which resembles huma n PAP, was found in aging (35 to 40 weeks) germ-free SCID-beige (scid/ scid-bg/bg) mice Spontaneous PAP was not observed in germ-free SCID mi ce. We describe the induction of PAP in SCID mice monoassociated with a pure culture of Candida albicans for 15 to 40 weeks. The gastrointes tinal tracts only are colonized and disseminated or pulmonary candidia sis does not occur. Another spontaneous form of PAP, designated type I I, was discovered in germ-free beige (bg/bg and bg/+) mice and in beig e-nude (bg/bg-nu/nu) mice, In this form of PAP, macrophages appear to be unable to digest the ingested phospholipoprotein complex and then a ccumulate in the alveolar spaces. These murine models should prove use ful in elucidating the relationships between immune deficiencies, infe ctions, and cytokine regulation of granulocyte and macrophage producti on and function in pulmonary alveolar proteinosis.