immune system
• in vitro, isolated bone marrow-derived macrophages (BMDMs) infected with methicillin-resistant Staphylococcus aureus (MRSA) show enhanced NLR-family pyrin domain-containing-3 (NLRP3) inflammasome activation with significantly greater NLRP3 protein levels, Caspase-1 (p20) and IL-1beta (p17) cleavage, apoptosis-associated speck-like protein (ASC) speck formation, and IL-1beta production than MRSA-infected wild-type BMDMs
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• in vitro, MRSA-infected BMDMs show significantly higher IL-1beta production than similarly infected wild-type BMDMs
• however, IL-6 and TNF secretion is similar to that in wild-type BMDMs after MRSA infection
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• MRSA-infected males show significantly higher plasma IL-1beta levels than MRSA-infected wild-type controls
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• at 12 h after i.v. MRSA injection, males show a markedly lower plasma fibrinogen level than MRSA-infected wild-type controls
• pretreatment with MCC950 before MRSA injection results in a significant increase of the plasma fibrinogen level
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• in vitro, MRSA-infected BMDMs show significantly higher IL-1beta production than similarly infected wild-type BMDMs
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• after i.v. MRSA injection, males show increased inflammatory cell infiltration in major organs (liver, lung, and kidney) and significantly higher NLRP3 protein levels in liver tissue and plasma IL-1beta levels than MRSA-infected wild-type controls
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• at 12 h after i.v. injection of MRSA (1 x 108 CFU/mouse), males show a significantly higher bacterial load in blood and major organs (liver, spleen, lung and kidney) as well as higher thrombus and inflammatory cell infiltration in the liver, lung, and kidney than MRSA-infected wild-type controls
• pretreatment with MCC950 (a specific inhibitor of NLRP3 inflammasome) 30 min before MRSA injection significantly improves coagulation and alleviates organ injury
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• males show increased susceptibility to MRSA-induced septic death with all mice dying within about 6 days of infection, unlike MRSA-infected wild-type controls
• pretreatment with MCC950 before MRSA injection significantly improves the 14-day survival rate in septic mice
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homeostasis/metabolism
• at 12 h after i.v. MRSA injection, males show a markedly higher D-dimer level in blood than MRSA-infected wild-type controls
• pretreatment with MCC950 before MRSA injection results in a significant reduction of the plasma D-dimer level
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• MRSA-infected males show significantly higher plasma IL-1beta levels than MRSA-infected wild-type controls
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• at 12 h after i.v. MRSA injection, males show a markedly lower plasma fibrinogen level than MRSA-infected wild-type controls
• pretreatment with MCC950 before MRSA injection results in a significant increase of the plasma fibrinogen level
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• at 12 h after i.v. MRSA injection, adult males show increased susceptibility to sepsis-induced disseminated intravascular coagulation (DIC), with significantly higher blood levels of thrombin-antithrombin complex (TAT) and plasminogen activator inhibitor 1 (PAI-1) than MRSA-infected wild-type controls
• pretreatment with MCC950 before MRSA injection significantly reduces blood levels of TAT and PAI-1 and improves overall sepsis-induced coagulation
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• at 12 h after i.v. MRSA injection, males show a markedly higher activated partial thromboplastin time (APTT) than MRSA-infected wild-type controls
• pretreatment with MCC950 before MRSA injection results in a significant reduction of the APTT
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• after i.v. MRSA injection, males show increased thrombus formation in major organs (liver, lung, and kidney), as determined by H&E staining
• pretreatment with MCC950 before MRSA injection reduces thrombus formation in liver, lung, and kidney
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hematopoietic system
• at 12 h after i.v. MRSA injection, males show a markedly lower platelet count than MRSA-infected wild-type controls
• pretreatment with MCC950 before MRSA injection results in a significant increase of the platelet count
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• in vitro, isolated bone marrow-derived macrophages (BMDMs) infected with methicillin-resistant Staphylococcus aureus (MRSA) show enhanced NLR-family pyrin domain-containing-3 (NLRP3) inflammasome activation with significantly greater NLRP3 protein levels, Caspase-1 (p20) and IL-1beta (p17) cleavage, apoptosis-associated speck-like protein (ASC) speck formation, and IL-1beta production than MRSA-infected wild-type BMDMs
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• in vitro, MRSA-infected BMDMs show significantly higher IL-1beta production than similarly infected wild-type BMDMs
• however, IL-6 and TNF secretion is similar to that in wild-type BMDMs after MRSA infection
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mortality/aging
• males show increased susceptibility to MRSA-induced septic death with all mice dying within about 6 days of infection, unlike MRSA-infected wild-type controls
• pretreatment with MCC950 before MRSA injection significantly improves the 14-day survival rate in septic mice
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