Esmon, C. T. Interactions between the innate immune and blood coagulation systems. Trends Immunol. 25, 536-542

Oklahoma Medical Research Foundation, Dept of Pathology, University of Oklahoma Health Sciences Center, and Howard Hughes Medical Institute, Oklahoma City 73104, USA.
Trends in Immunology (Impact Factor: 10.4). 11/2004; 25(10):536-42. DOI: 10.1016/
Source: PubMed


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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    • "Chicken fibrinogen (Fbg) is thus considered a biomarker of persistent infections in routine haematological and biochemical screening tests (Hawkey & Hart, 1988). Haemostatic alterations, as part of the innate immune response, have been described in response to acute inflammation during severe infection or trauma disturbing the delicate balance of pro-coagulant, fibrinolytic and anticoagulant factors, which can lead to development of disease complications such as disseminated intravascular coagulation (DIC) and microvascular thrombosis, described in mammalian species (Esmon, 2004; Levi & van der Poll, 2010; O'Brien, 2012). Although the basic mechanism of haemostasis and clot formation is considered similar in all vertebrates, including birds (Davidson et al., 2003; Gentry, 2004), few specific studies have been focused on avian haemostasis. "
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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.
    Full-text · Article · Jul 2014 · Avian Pathology
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    • "The coagulation system is an important host defense system in lower organisms, and there is also significant interaction between innate immunity and coagulation in higher vertebrates (Esmon, 2004). A recent study suggested that neutrophil serine proteases play an important role in the reciprocal coupling between innate immunity and coagulation in mice (Massberg et al., 2010; Fig. 3 C). "
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    ABSTRACT: Neutrophils have long been considered simple suicide killers at the bottom of the hierarchy of the immune response. That view began to change 10-20 yr ago, when the sophisticated mechanisms behind how neutrophils locate and eliminate pathogens and regulate immunity and inflammation were discovered. The last few years witnessed a new wave of discoveries about additional novel and unexpected functions of these cells. Neutrophils have been proposed to participate in protection against intracellular pathogens such as viruses and mycobacteria. They have been shown to intimately shape the adaptive immune response at various levels, including marginal zone B cells, plasmacytoid dendritic cells and T cell populations, and even to control NK cell homeostasis. Neutrophils have been shown to mediate an alternative pathway of systemic anaphylaxis and to participate in allergic skin reactions. Finally, neutrophils were found to be involved in physiological and pathological processes beyond the immune system, such as diabetes, atherosclerosis, and thrombus formation. Many of those functions appear to be related to their unique ability to release neutrophil extracellular traps even in the absence of pathogens. This review summarizes those novel findings on versatile functions of neutrophils and how they change our view of neutrophil biology in health and disease.
    Preview · Article · Jul 2013 · Journal of Experimental Medicine
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    • "This will enable molecular dissection of the pathways involved in the urochordate innate immunity. Coagulation and innate immunity, not only are highly integrated [1], [39], exhibiting crosstalk features (i.e., complement and coagulation associations; 40) but may share an ancestral molecular stem early in eukaryotic evolution. "
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    ABSTRACT: The colonial ascidian Botryllus schlosseri expresses a unique allorecognition system. When two histoincompatible Botryllus colonies come into direct contact, they develop an inflammatory-like rejection response. A surprising high number of vertebrates' coagulation genes and coagulation-related domains were disclosed in a cDNA library of differentially expressed sequence tags (ESTs), prepared for this allorejection process. Serine proteases, especially from the trypsin family, were highly represented among Botryllus library ortholgues and its "molecular function" gene ontology analysis. These, together with the built-up clot-like lesions in the interaction area, led us to further test whether a vertebrate-like clotting system participates in Botryllus innate immunity. Three morphologically distinct clot types (points of rejection; POR) were followed. We demonstrated the specific expression of nine coagulation orthologue transcripts in Botryllus rejection processes and effects of the anti-coagulant heparin on POR formation and heartbeats. In situ hybridization of fibrinogen and von Willebrand factor orthologues elucidated enhanced expression patterns specific to histoincompatible reactions as well as common expressions not augmented by innate immunity. Immunohistochemistry for fibrinogen revealed, in naïve and immune challenged colonies alike, specific antibody binding to a small population of Botryllus compartment cells. Altogether, molecular, physiological and morphological outcomes suggest the involvement of vertebrates-like coagulation elements in urochordate immunity, not assigned with vasculature injury.
    Full-text · Article · Feb 2008 · PLoS ONE
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