Interactions between the innate immune and blood coagulation systems.
ABSTRACT Blood coagulation and inflammation are universal responses to infection and there is crosstalk between inflammation and coagulation that can either amplify or dampen the responses. Loss of appropriate interactions between these systems probably contributes to morbidity and mortality in infectious diseases. For instance, inflammatory cytokines and leukocyte elastase can downregulate natural anticoagulant proteins that help to maintain endothelial-cell integrity, control clotting, inhibit vasoactive peptides and dampen leukocyte infiltration into the vessel wall. This Review will summarize our current understanding of the mechanisms involved in the crosstalk between these two important systems.
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ABSTRACT: Streptococcuszooepidemicus has recently been shown as a severe pathogen in layer chickens where it is able to cause serious lesions in the vascular system. To evaluate the hemostatic response, ten layer chickens were inoculated intravenously with S. zooepidemicus. Four hypotheses were tested: that the infection-induced inflammation would 1) increase plasma fibrinogen (Fbg) concentration, 2) prolong prothrombin time (PT) 3) prompt hypercoagulability or hypocoagulability as assessed by whole-blood thromboelastography (TEG), and 4) that a possible correlation would exist between one of the TEG values and Fbg/PT. Each parameter was measured at days 1, 3 and 6 post-inoculation (p.i.), and compared to the values at day 0 from each individual bird and to values obtained from non-infected control chickens (n = 10). In the infected chickens, the mean (±SE) of Fbg was higher at day-3 (9.4 ± 1.4 gram/liter) and day-6 (8.0 ± 0.7 g/l) and the PT was prolonged at day-6 p.i. (168.1 ± 21.0 seconds) compared to the day-0 standards (2.6 ± 0.2 g/l, 104.6 ± 2.0 sec, respectively) (P < 0.05). The majority of infected chickens demonstrated a hypercoagulable TEG result with increased mean values of clot-formation rate/α-angel and maximal amplitude/MA of TEG tracing at day-3 (83.1 ± 0.7 degrees, 83.8 ± 1.4 millimeter) and day-6 p.i. (84.0 ± 0.4 deg, 89.8 ± 1.0 mm) compared to the day-0 values (75.8 ± 2.2 deg, 66.9 ± 1.4 mm, respectively) (P < 0.05). In control birds, the means of Fbg (1.5 ± 0.1 g/l), PT (79.4 ± 6.4 sec), TEG-α (76.7 ± 1.5 deg) and TEG-MA (64.0 ± 2.3 mm) were lower at day-6 compared with values observed for the infected chickens (P < 0.05). A negative correlation-coefficient ( 0.71) was found between clot-formation time/TEG-K and Fbg at day-1 in the control group (P = 0.02). In conclusion, infection with S. zooepidemicus following intravenous injection in layer chickens induced hemostatic alterations including hyperfibrinogenemia, prolonged PT, and hypercoagulability as measured by increased TEG-α and TEG-MA.Avian Pathology 07/2014; DOI:10.1080/03079457.2014.938608 · 2.04 Impact Factor
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ABSTRACT: Understanding the pathomechanism of cancer is of primary interest in medical research (Trosko and Rauch, 1998; Bjerkvig et al., 2005). In the past century, several mechanisms were proposed. It was hypothesized that cancer arises from a single cell that loses its differentiated state through sequential mutations. This initiation-promotion-progression concept explains the steps in a sequential process. Later, this hypothesis led to the mutagenic and recently the oncogenic theories, which hypothesize that defects in tumor suppressor genes are responsible for the development of cancer. The impairment of cell-to-cell communication as a cause of cancer has also been postulated. One fascinating finding is that immunosuppressive cytotoxic antineoplastic therapies may, on occasion, cause the regression of a clinically established cancer. At first, applying this as a therapeutic strategy may seem counterintuitive, considering the fundamental role of the immune system in protecting the body against infectious organisms and aberrant cells. In addition, cancer itself is frequently immunosuppressive, so exacerbating a pre-existing immunosuppression may not seem like a rational strategy.12/2007: pages 161-177;
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ABSTRACT: Bacillus anthracis must overcome host innate immune defences to establish a systemic anthrax infection. This is facilitated in part by lethal toxin (LT), a secreted virulence factor that consists of a cell-binding moiety, protective antigen (PA), and an enzymatic moiety, lethal factor (LF). PA binds cells through protein receptors and mediates the delivery of LF to the cytosol. LF is a protease that cleaves amino-terminal fragments from mitogen-activated protein kinase kinases (MAPKKs), preventing phosphorylation of their downstream targets. Here we report that LT reduces the amount of interleukin (IL)-8 produced and secreted by human endothelial cells. The reduction of IL-8 levels by LT was not attributable to reduced expression from the IL-8 promoter, but resulted from destabilization of IL-8 mRNA. Destabilization by LT was mediated through the 3' untranslated region of the IL-8 transcript and could be mimicked by pharmacological inhibitors of MAPK pathways. LT diminished the induction of IL-8 mRNA and protein by lipopolysaccharide, indicating that the toxin can impair the ability of these cells to initiate an immune response. Destabilization of a cytokine transcript represents a new interference strategy used by either a bacterial or viral pathogen to reduce cytokine expression and may help B. anthracis to evade host immune defences.Cellular Microbiology 02/2006; 8(1):130-8. DOI:10.1111/j.1462-5822.2005.00606.x · 4.82 Impact Factor