Esmon, C. T. Interactions between the innate immune and blood coagulation systems. Trends Immunol. 25, 536-542
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.
- "The severe hepatic tissue damage (Figs. 2, 3 and 7A) likely caused abnormalities in liver function, such as the abnormal synthesis of various procoagulant proteins and the abnormal clearance of activated coagulation proteins, probably leading to DIC . Furthermore, the mechanisms underlying the cross-talk between innate immunity and blood coagulation systems have become increasingly clear [28,29]. In this regard, Niessen et al. recently presented evidence that in dendritic cells protease-activated receptor 1 signalling cross-talks with a downstream sphingosine-1 phosphate axis, coupling coagulation and inflammation . "
[Show abstract] [Hide abstract] ABSTRACT: Background Coagulation and complement activation represent key events in ischaemia–reperfusion-induced renal injury leading to delayed graft function (DGF). It is still unclear whether the coagulation cascade may also influence the acquired immunity. The aim of the present study was to investigate the expression of protease-activated receptor 1 (PAR-1), the main thrombin receptor, by graft-infiltrating dendritic cells (DCs), and to evaluate whether thrombin may influence DCs complement production and T-cell response.0Comments 0Citations
- "In addition, Th1 cells have been suggested to play a key role in the development of graft rejection , thus representing the ideal bridge between these conditions. In conclusion, although the specific molecular interactions between the coagulation and the complement cascades have been described in several models [32, 33], in the present study, we demonstrated for the first time a specific synergic effect in the induction of a Th1 immune response by thrombin and complement factors in the settings of DGF patients. This synergic effect involving the two main humoral components of the innate immunity on the adaptative immune response may represent one of the pathogenic mechanisms underlying the association between DGF and acute graft rejection, an event often observed in renal transplantation. "
[Show abstract] [Hide abstract] ABSTRACT: Aminopeptidases are part of the arsenal of virulence factors produced by bacterial pathogens that inactivate host immune peptides. Mycoplasma hyopneumoniae is a genome-reduced pathogen of swine that lacks the genetic repertoire to synthesize amino acids and relies on the host for availability of amino acids for growth. M. hyopneumoniae recruits plasmin(ogen) onto its cell surface via the P97 and P102 adhesins and the glutamyl aminopeptidase MHJ_0125. Plasmin plays an important role in regulating the inflammatory response in the lungs of pigs infected with M. hyopneumoniae. We show that recombinant MHJ_0461 (rMHJ_0461) functions as a leucine aminopeptidase (LAP) with broad substrate specificity for leucine, alanine, phenylalanine, methionine and arginine and that MHJ_0461 resides on the surface of M. hyopneumoniae. rMHJ_0461 also binds heparin, plasminogen and foreign DNA. Plasminogen bound to rMHJ_0461 was readily converted to plasmin in the presence of tPA. Computational modelling identified putative DNA and heparin-binding motifs on solvent-exposed sites around a large pore on the LAP hexamer. We conclude that MHJ_0461 is a LAP that moonlights as a multifunctional adhesin on the cell surface of M. hyopneumoniae.0Comments 4Citations
- "Several bacterial species manipulate host defences by commandeering host plasminogen . Many cell surface proteins bind plasminogen and facilitate its conversion to plasmin by enhancing the accessibility to host plasminogen activating enzymes urokinase plasminogen activator and tPA or by producing bacterial surface-associated activators that interact with plasminogen and activate it by complex formation . rMHJ_0461 bound plasminogen in a concentration-dependent manner (figure 7a). "