Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice lacking granulocyte colony-stimulating factor (G-CSF) are neutropenic with reduced hematopoietic progenitors in the bone marrow and spleen, whereas those lacking granulocyte-macrophage colony-stimulating factor (GM-CSF) have impaired pulmonary homeostasis and increased splenic hematopoietic progenitors, but unimpaired steady-state hematopoiesis. These contrasting phenotypes establish unique roles for these factors in vivo, but do not exclude the existence of additional redundant functions. To investigate this issue, we generated animals lacking both G-CSF and GM-CSF. In the process of characterizing the phenotype of these animals, we further analyzed G-CSF- and GM-CSF-deficient mice, expanding the recognized spectrum of defects in both. G-CSF-deficient animals have a marked predisposition to spontaneous infections, a reduced long-term survival, and a high incidence of reactive type AA amyloidosis. GM-CSF-deficient mice have a modest impairment of reproductive capacity, a propensity to develop lung and soft-tissue infections, and a similarly reduced survival as in G-CSF-deficient animals. The phenotype of mice lacking both G-CSF and GM-CSF was additive to the features of the constituent genotypes, with three novel additional features: a greater degree of neutropenia among newborn mice than in those lacking G-CSF alone, an increased neonatal mortality rate, and a dominant influence of the lack of G-CSF on splenic hematopoiesis resulting in significantly reduced numbers of splenic progenitors. In contrast to newborn animals, adult mice lacking both G-CSF and GM-CSF exhibited similar neutrophil levels as G-CSF-deficient animals. These findings demonstrate that the additional lack of GM-CSF in G-CSF-deficient animals further impairs steady-state granulopoiesis in vivo selectively during the early postnatal period, expand the recognized roles of both G-CSF and GM-CSF in vivo, and emphasize the utility of studying multiply deficient mouse strains in the investigation of functional redundancy.
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PMID:Mice lacking both granulocyte colony-stimulating factor (CSF) and granulocyte-macrophage CSF have impaired reproductive capacity, perturbed neonatal granulopoiesis, lung disease, amyloidosis, and reduced long-term survival. 937 84

Evidence shows that tissue macrophages (MPhis), in mice undergoing AA amyloidosis, endocytose acute-phase humoral serum amyloid A (SAA) and traffic it to lysosomes where it is degraded. Incomplete degradation of SAA leads to intracellular nascent AA fibril formation. In vitro, cathepsin (Cat) B is known to generate amyloidogenic SAA derivatives, whereas Cat D generates non-amyloidogenic SAA derivatives, and interferon (IFN-gamma)-treated MPhis show selective increase in Cat B concentration, a factor conducive to AA amyloidogenesis. To understand the cumulative effect of these factors in AA amyloidosis, humoral levels of SAA, IFN-gamma, tumour necrosis factor (TNF-alpha) and granulocyte-macrophage colony-stimulating factor were determined in azocasein (AZC)-treated CD-1 mice. We correlated these responses with the spatio-temporal distribution of SAA, Cat B- and Cat D-immunoreactive splenic reticuloendothelial (RE) cells. AZC-treated CD-1 mice similar to that of A/J mice showed partial amyloid resistance; their peak humoral IFN-gamma and SAA responses overlapped during the pre-amyloid phase. Unexpectedly, Cat D immunoreactivity (IR), instead of Cat B IR, was predominant in the splenic RE cells, indicating an apparent lack of causal relationship between IFN-gamma-mediated increase in Cat B expression. Partial amyloid resistance in CD-1 mice, probably a genetic trait, may be linked to high levels of Cat D expression, causing a delay in nascent AA fibril formation.
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PMID:Humoral proinflammatory cytokine and SAA generation profiles and spatio-temporal relationship between SAA and lysosomal cathepsin B and D in murine splenic monocytoid cells during AA amyloidosis. 1487 Dec 93