Mice lacking both macrophage- and granulocyte-macrophage colony-stimulating factor have macrophages and coexistent osteopetrosis and severe lung disease.
نویسندگان
چکیده
Mice deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF, CSF-1) were generated by interbreeding GM-CSF-deficient mice generated by gene targeting (genotype GM-/-) with M-CSF-deficient osteopetrotic mice (genotype M-/-, op/op). Mice deficient in both GM-CSF and M-CSF (genotype GM-/-M-/-) are viable and have coexistent features corresponding to mice deficient in either factor alone. Like M-CSF-deficient mice, they have osteopetrosis and are toothless because of failure of incisor eruption. Like GM-CSF-deficient mice, they have a characteristic alveolar-proteinosis-like lung pathology, but it is more severe than that of GM-CSF-deficient mice and is often fatal. In particular, in GM-/-M-/- mice the accumulation of lipo-proteinaceous alveolar material is more marked, and bacterial pneumonic infections are more prevalent and more extensive, particularly involving Gram-negative bacteria. Neutrophilia consistently accompanies pulmonary infections, and some older GM-/-M-/- mice have polycythemia. Survival of GM-/-M-/- mice is significantly reduced compared with mice deficient in either factor alone, and all GM-/-M-/- mice have broncho- or lobar-pneumonia at death. These observations indicate that in vivo, M-CSF is involved in modulating the consequences of GM-CSF deficiency in the lung. Interestingly, GM-/-M-/- mice have circulating monocytes at levels comparable with those in M-CSF-deficient mice and the diseased lungs of all GM-/-M-/- mice contain numerous phagocytically active macrophages, indicating that in addition to GM-CSF and M-CSF, other factors can be used for macrophage production and function in vivo.
منابع مشابه
RAPID COMMUNICATION Mice Lacking Both Macrophage- and Granulocyte-Macrophage Colony- Stimulating Factor Have Macrophages and Coexistent Osteopetrosis and Severe Lung Disease
Mice deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF, CSF-1) were generated by interbreeding GMCSF-deficient mice generated by gene targeting (genotype GM-/-) with M-CSF-deficient osteopetrotic mice (genotype M-/-, op/op). Mice deficient in both GM-CSF and MCSF (genotype GM-/-"/-) are viable and have coexistent features corr...
متن کاملTHE ROLE OF ALVEOLAR MACROPHAGES IN THE PRODUCTION OF COLONY –STIMULATING FACTOR BY THE LUNG
The role of alveolar macrophages in the production of granulocyte/ macrophage colony-stimulating factor(s) by the rat lung was investigated. Lavaged lungs, when incubated at proper weight per volume of culture medium, produced the same amount of colony-stimulating factor as unlavaged ones. Both lavaged and unlavaged lungs produced similar types of colony-stimulating factor (s). Prolonged i...
متن کاملComparison of T7- and Lac-Based Systems for the Periplasmic Expression of Human Granulocyte Macrophage Colony Stimulating Factor in Escherichia coli
متن کامل
Granulocyte-macrophage colony-stimulating factor is not responsible for the correction of hematopoietic deficiencies in the maturing op/op mouse.
Osteopetrotic (op/op) mice are characterized by an autosomal recessive inactivating mutation resulting in the absence of biologically active colony-stimulating factor-1 (CSF-1). Consequently, young op/op mice have a severe deficiency of macrophages and osteoclasts resulting in excessive bone formation, occlusion of the marrow cavity, and reduced marrow hematopoietic activity. Recently, we showe...
متن کاملExpression and Secretion of Human Granulocyte Macrophage-Colony Stimulating Factor Using Escherichia coli Enterotoxin I Signal Sequence
With the aim of the secretion of human granulocyte macrophage-colony stimulating factor (hGM-CSF) in Escherichia coli, hGM-CSF cDNA was fused in-frame next to the signal sequence of ST toxin (ST-I) of exteroxigenic E. coli, containing 53 or 19 amino acids of signal peptide. The fused STsig::hGM-CSF coding fragments were inserted into a T7-based expression plasmid. The recombinant plasmids were ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Blood
دوره 84 1 شماره
صفحات -
تاریخ انتشار 1994