immune system
• neutrophils exhibit an unusual hypermature morphology characterized by nuclear hypersegmentation and blebbing
• neutrophil markers are aberrantly expressed with decreases in Ly-6G and Mac-1 expression in the periphery and increases of 7/4 expression in the bone marrow
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• the number of granulocytes are found in the bone marrow is increased by more than a third
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• there are higher numbers of neutrophils in the blood with 5.76 x 105 cells per ml found versus 2.5 x 105 in controls
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• granulocytes have higher rates of proliferation with approximately 2-fold more granulocytes actively proliferating in the bone marrow than in controls
• mutant bone marrow cells generate 2.3-fold more colonies than wild-type bone marrow in methylcellulose cultures with granulocyte colony stimulating factor
• competitive bone marrow chimera experiments confirm that granulocytes develop into neutrophils at a faster rate
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• neutrophils are hypersensitive to activating stimuli
• neutrophils have a 50% higher oxidative burst than controls upon low-dose PMA stimulation
• neutrophils display 25% higher killing when co-cultured with Candida albicans
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• low-dose LPS administration leads to distress caused by endotoxaimia
• after LPS administration, mice have significantly higher levels of aspartate aminotransferase, blood urea nitrogen and creatine kinase, indicative of considerable widespread tissue damage
• hepatocyte necrosis and intralobular haemorrhage are also observed after LPS administration
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• mice over 1.2 years of age consistently display inflammatory lung pathology characterized by areas of atelectasis, increased cellularity within the parenchyma, and inflammatory infiltration into the interstitium
• neutrophils are the most prominent cell type in this infiltrate
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hematopoietic system
• neutrophils exhibit an unusual hypermature morphology characterized by nuclear hypersegmentation and blebbing
• neutrophil markers are aberrantly expressed with decreases in Ly-6G and Mac-1 expression in the periphery and increases of 7/4 expression in the bone marrow
|
• the number of granulocytes are found in the bone marrow is increased by more than a third
|
• there are higher numbers of neutrophils in the blood with 5.76 x 105 cells per ml found versus 2.5 x 105 in controls
|
• granulocytes have higher rates of proliferation with approximately 2-fold more granulocytes actively proliferating in the bone marrow than in controls
• mutant bone marrow cells generate 2.3-fold more colonies than wild-type bone marrow in methylcellulose cultures with granulocyte colony stimulating factor
• competitive bone marrow chimera experiments confirm that granulocytes develop into neutrophils at a faster rate
|
• neutrophils are hypersensitive to activating stimuli
• neutrophils have a 50% higher oxidative burst than controls upon low-dose PMA stimulation
• neutrophils display 25% higher killing when co-cultured with Candida albicans
|
respiratory system
• mice over 1.2 years of age consistently display inflammatory lung pathology characterized by areas of atelectasis, increased cellularity within the parenchyma, and inflammatory infiltration into the interstitium
• neutrophils are the most prominent cell type in this infiltrate
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cellular
• neutrophils exhibit an unusual hypermature morphology characterized by nuclear hypersegmentation and blebbing
• neutrophil markers are aberrantly expressed with decreases in Ly-6G and Mac-1 expression in the periphery and increases of 7/4 expression in the bone marrow
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