The speed of the host response is striking. Within the first 30 min of infection with an outbreak strain of S. aureus or another Gram-positive organism, Bacillus cereus, platelet aggregates are bound to Kupffer cells in the liver (43, 75). These aggregates can help enhance bacterial capture and limit bacterial dissemination, demonstrating the potential value of platelet interactions with host cells in host defense. Several studies using a P. aeruginosa-induced model of ARDS have evaluated the pro-coagulant imbalance during acute lung injury that has been associated with decreased fibrinolytic activity (67). These models highlight the capacity of early fibrin formation to limit damage, but its potential to harm if it persists (76). This led to the proposal that modulation of hemostasis, either by administration of recombinant human antithrombin (rhAT) or recombinant human activated protein C (rhAPC), may restore the fibrinolytic activity, then limiting the amount of inflammation (67, 76). Administration of rhAPC treatment or fibrin-derived peptides (Bβ 15-42) can exert a protective effect during acute lung injury (ALI), without modifying the inflammatory response to P. aeruginosa nor the bacterial clearance (77, 78). Moreover, in a different model of pneumonia induced by K. pneumoniae, overexpression of human tissue-type plasminogen activator (t-PA) was associated with a higher level of fibrinolysis in the lungs and decreased thrombus formation in the liver and subsequent improvements in survival of the host (68). These studies show the importance of fibrinolysis during infection and the roles coagulation/fibrinolytic factors can play in severe infections depending on the location of the infection and the pathogen.
As mentioned previously, most animal models of sepsis use Gram-negative bacteria or their endotoxins to evaluate coagulopathy. A limitation of these models is that they provoke an acute endotoxemia, rather than a sustained infection. Notwithstanding this temporal constraint, these models have been used to evaluate the potential for thrombosis to aid host defense. After systemic infection of neutrophil serine protease-deficient mice with relatively high doses of E. coli (3.2 108 CFU), fibrin deposition and restriction of bacteria within the sinusoid vasculature is reduced and there is an increase in bacteria within tissues (31). Since neutrophil proteases are essential to induce NETs, the authors concluded that the reduction in fibrin deposition (microthrombi) is directly responsible for bacterial spreading into the liver. Whilst indicative of a role of NETs in restricting bacterial dissemination, other roles for serine proteases may also contribute to these effects.
So what separated the Brougham LS from the standard Brougham In a word, more. More gingerbread primarily, consisting of a padded landau vinyl top with LS-monogrammed opera windows and opera lamps in the B-pillars (but of course). The interior was the same as the regular Brougham, so this was primarily an exterior decor package. 153554b96e