Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031154 (peritonitis)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to investigate the mechanism for hyperfibrinolysis in the ascites associated with peritonitis carcinomatosa. Various combinations of mouse MM2 ascites tumor (MAT) and mouse peritoneum (Mpr) and plasminogen (Plg) were incubated in medium 199 and the fibrinolytic activity of each preparation was assayed. 1) Among the preparations, the preparation of MAT plus Mpr plus Plg showed particularly high fibrinolytic activity. This suggests that plasminogen activator (PA) production is initiated by MAT together with Mpr. 2) Equal volumes of the ultrafiltrate and the concentrate of supernatant from MAT were each separately treated with a Mpr plus Plg preparation and incubated. The fibrinolytic activity of the ultrafiltrate was 10 times as great as that of the concentrate. 3) The ultrafiltrate of MAT was extracted in turn with petroleum ether, ether and hexane. The fibrinolytic activity of the petroleum ether and hexane extracts was higher than that of the ether extracts. These results suggest that MAT has a low polarity, low molecular weight, and lipid like substance (inducer of PA,IPA), which stimulates the Mpr to release PA.
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PMID:[Studies on fibrinolysis and ascites accumulation associated with peritonitis carcinomatosa--inducer of plasminogen activator (IPA) in malignant ascites tumor]. 294 4

Postsurgical abdominal adhesions and their sequelae continue to present major clinical and medicoeconomic problems. A complex network of mediators and responses affecting at least five interrelated biological systems, including the fibrinolytic system, are involved in the pathogenesis of postsurgical adhesions. The fibrinolytic system degrades fibrin through the action of the enzyme plasmin, which is stored as the inactive substrate plasminogen. Fibrinolysis, by mediating fibrin degradation, appears to play a pivotal role in adhesiogenesis. Tissue-type plasminogen activator (tPA) is the chief plasminogen activator in the blood, but its activity is restricted by plasminogen activating inhibitors type 1 (PAI-1) and type 2 (PAI-2). Inadequate peritoneal fibrinolysis may result from decreased tPA, increased PAI-1 and PAI-2, or both. The causal relationship between a reduction in fibrinolytic capacity and the formation of adhesions has been demonstrated in animals. In human studies, plasminogen activator activity (PAA) was significantly reduced in peritoneal biopsies from patients with peritonitis compared with those from normal patients. During surgery, PAA declined significantly in both normal and inflamed peritoneum. tPA was responsible for about 95% of PAA. Reduced fibrinolysis in human peritoneum associated with peritonitis and abdominal surgery correlates with increased adhesion formation and may thus be an important early biochemical event leading to adhesion formation. The regulation of plasmin-mediated fibrin degradation in the peritoneal cavity is poorly understood. However, new insights in the cellular distribution of fibrinolytic components in peritoneal tissue suggest that the mesothelium appears to have a principal role in fibrin regulation in the peritoneal cavity and in the early formation of adhesions.
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PMID:The role of fibrinolysis in adhesion formation. 907 49

Vascular cell adhesion and migration, proliferation or differentiation are cellular responses that are induced by haemostatic factors of the urokinase/plasminogen activation complex, but the respective underlying mechanisms are largely undefined. The direct and indirect contributions of the urokinase-type plasminogen activator receptor (uPAR) system in inflammatory processes, as they relate to recruitment of leukocytes, define novel functions and could serve as therapeutic targets for related vasculopathies. The presence of uPAR plays a crucial role in beta2-integrin-mediated adhesion of leukocytes; uPAR also directly mediates leukocyte adhesion to vitronectin, a multifunctional adhesion protein that is associated with the extracellular matrix. The latter process is inhibited by plasminogen activator inhibitor-1. Both beta2-integrin- and uPAR-dependent processes are activated by Zn2+ and are blocked by high-molecular-mass kininogen. Domain 5 of kininogen was identified, in particular, as an anti-adhesive component with a potent anti-inflammatory action in a peritonitis mouse model. In patients with acute myocardial infarction, elevated expression of uPAR on monocytes resulted in their increased adherence to the endothelium, which indicates a possible role of the uPAR system in monocyte recruitment to the infarcted area. Urokinase-type plasminogen activator was identified as a potent mitogen for vascular smooth muscle cells, an observation that was independent of the presence of uPAR and its proteolytic activity. Taken together, these results strongly suggest an essential role for the uPAR system in acute inflammation as well as in chronic degenerative vascular processes such as atherosclerosis. Targeting the uPAR system may allow specific therapeutic intervention in vascular pathologies.
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PMID:Haemostatic factors occupy new territory: the role of the urokinase receptor system and kininogen in inflammation. 1202 45

The clinical, immunobiochemical and hemostasiological parameters of the systemic inflammatory response (SIR) were studied in 51 patients with diffusive peritonitis. The study showed that lactoferrin, plasminogen/plasmin and alpha 2-macroglobulin can be used, in a set, as informative indices of SIR. A reduced content of lactoferrin, a smaller concentration of proteases inhibitor alpha 2-macroglobulin and a higher relation between plasminogen and plasmin correlate with an unfavorable outcome of the disease beginning from the 1st postoperative day. An activity of Willebrandt's factor is a diagnostic and prognostic marker, which determines a lesion to the endothelium system.
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PMID:[Characteristics of certain components of the systemic inflammatory reaction in patients with diffusive peritonitis]. 1293 39

Angiogenesis and inflammation are closely related biologic processes in wound healing and the responses to vascular injury as well as in cardiovascular diseases; however, the molecular connections are poorly defined. In particular, it is yet unclear whether endogenous factors can regulate both angiogenesis and inflammation. Here, we show that the endogenous angiogenesis inhibitor, angiostatin (containing kringle domains 1-4 of plasminogen), serves an anti-inflammatory role, since the kringles 1-3 and its kringle 4 directly interact with leukocyte beta1- and beta2-integrins, respectively. In particular, a specific interaction between kringle 4 and alphaMbeta2-integrin (Mac-1) but not leukocyte function antigen 1 (LFA-1) was identified. Angiostatin thereby inhibited beta1- and beta2-integrin-mediated adhesion of leukocytes to extracellular matrix proteins and the endothelium as well as their transmigration through the endothelium in vitro. Moreover, angiostatin blocked the peritonitis-induced neutrophil emigration in vivo. In addition, through its interaction with Mac-1, angiostatin reduced activation of the proinflammatory transcription factor nuclear factor kappaB (NFkappaB), as well as the NFkappaB-related expression of tissue factor, a potent initiator of hemostasis following vascular injury. Finally, angiostatin forms were generated in vivo following skin injury/inflammation and were detectable during the following entire period of wound healing peaking at the terminal phase of the healing process. Taken together, over and above inhibition of neovascularization, angiostatin was identified as an antiadhesive/anti-inflammatory substance. These observations could provide the basis for new therapeutic applications of angiostatin to target chronic inflammatory processes in different pathologic situations.
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PMID:Angiostatin is a novel anti-inflammatory factor by inhibiting leukocyte recruitment. 1538 57

To evaluate the predictive value of protein C as a marker of severity in patients with diffuse peritonitis and abdominal sepsis, protein C levels were repeatedly determined and compared with serum levels of antithrombin III, plasminogen, alpha(2)-antiplasmin, Plasminogen activator inhibitor, D-dimer, C1-inhibitor, high molecular weight kininogen, and the C5a, C5b-9 fragments of the complement system. We carried out a prospective study from 44 patients with severe peritonitis confirmed by laparotomy and 15 patients undergoing elective ventral hernia repair who acted as controls. Analyzed biochemical parameters were determined before operations and on days 1, 2, 3, 5, 7, 10, and 14 after operations. For the study group, preoperative average protein C level was significantly lower in the patients who developed septic shock in the late course of the disease, with lethal outcome, than in the patients with severe peritonitis and sepsis who survived (p = 0.0001). In non-survivors, protein C activity remained decreased below 70%, whereas the course of survivors was characterized by increased values that were significantly higher (p < 0.03) at every time point than in those patients who died. Protein C was of excellent predictive value and achieved a sensitivity of 80% and a specificity of 87.5% in discriminating survivors from non-survivors within the first 48 hours of the study (AUC-0.917; p < 0.001), with a "cut-off" level of 66.0%. As for the control group, throughout the study period, protein C activity was permanently maintained within the range of normal, with significant differences with reference to the study group (p < 0.01). These results suggest that protein C represents a sensitive and early marker for the prediction of severe septic complications during diffuse peritonitis, and of outcome.
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PMID:Protein C as an early marker of severe septic complications in diffuse secondary peritonitis. 1588 Feb 75

There are two plasminogen activators (PAs), urokinase type-PA (u-PA) and tissue type-PA (t-PA). While u-PA is considered to be involved in cellular migration and tissue remodeling and t-PA in fibrinolysis, this distinction is not always clear-cut. With the use of u-PA and t-PA gene deficient mice (u-PA-/- and t-PA-/- mice, respectively) we have assessed the role of each PA in acute peritonitis. The cellular infiltrate in both thioglycolate- and antigen-induced peritoneal exudates was unaffected in u-PA-/- mice; in contrast, in t-PA-/- mice, the macrophage numbers, particularly of the Mac-1(hi) population, in the peritoneal cavity by day 4 were significantly reduced compared to wild-type mice. However, examination of the peritoneal wall revealed in fact increased numbers of macrophages adhering on/in the cavity lining at all time points studied; in addition, increased fibrin(ogen) staining was observed for these mice. The reduced macrophage numbers in the peritoneal cavities of t-PA-/- mice could be increased by administration of plasmin or t-PA prior to harvesting the thioglycolate-elicited exudates. These results suggest that t-PA and not u-PA is the PA controlling fibrinolysis in murine peritonitis. In its absence macrophages adhere to the accumulated fibrin(ogen) on/in the cavity wall lining, most likely via Mac-1 binding, thus affecting migration into and/or out of the peritoneal cavity. They also highlight the need to examine both the peritoneal cavity and wall in order to monitor accurately the extent of a peritoneal inflammatory reaction. Peritoneal inflammation in t-PA-/- mice represents a useful model to study the progression of intra-abdominal adhesions during surgery and clinical peritonitis.
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PMID:The effect of tissue type-plasminogen activator deletion and associated fibrin(ogen) deposition on macrophage localization in peritoneal inflammation. 1660 37

Sepsis is associated with enhanced production of tissue-type plasminogen activator (tPA). We investigated the function of endogenous tPA in the immune responses to Escherichia coli-induced abdominal sepsis using tPA gene-deficient (tPA(-/-)) and normal wild-type (WT) mice. tPA(-/-) mice demonstrated an impaired defense against E. coli peritonitis as indicated by higher bacterial loads at the primary site of the infection, enhanced dissemination, and reduced survival. The protective function of tPA was independent of plasmin since plasminogen gene-deficient (Plg(-/-)) mice were indistinguishable from WT mice. Relative to WT mice, tPA(-/-) mice demonstrated similar neutrophil counts in the peritoneal cavity despite much higher bacterial loads and higher local concentrations of neutrophil attracting chemokines, suggesting a reduced migratory response. In line, tPA(-/-) mice demonstrated a reduced thioglycolate-induced neutrophil influx into the peritoneal cavity and i.p. injection of WT mice with a replication-defective adenoviral vector expressing tPA caused an enhanced cell migration to the peritoneal cavity during E. coli peritonitis. These findings identify a novel protective function of tPA in abdominal sepsis caused by E. coli that seems independent of its role in the generation of plasmin.
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PMID:Endogenous tissue-type plasminogen activator is protective during Escherichia coli-induced abdominal sepsis in mice. 1681 77

Localization of plasmin on macrophages and activation of pro-MMP-9 play key roles in macrophage recruitment in the inflammatory response. These functions are promoted by plasminogen receptors exposing C-terminal basic residues on the macrophage surface. Recently, we identified a novel transmembrane plasminogen receptor, Plg-R(KT), which exposes a C-terminal lysine on the cell surface. In the present study, we investigated the role of Plg-R(KT) in macrophage invasion, chemotactic migration, and recruitment. Plg-R(KT) was prominently expressed in membranes of human peripheral blood monocytes and monocytoid cells. Plasminogen activation by urokinase-type plasminogen activator (uPA) was markedly inhibited (by 39%) by treatment with anti-Plg-R(KT) mAb. Treatment of monocytes with anti-Plg-R(KT) mAb substantially inhibited invasion through the representative matrix, Matrigel, in response to MCP-1 (by 54% compared with isotype control). Furthermore, chemotactic migration was also inhibited by treatment with anti-Plg-R(KT) mAb (by 64%). In a mouse model of thioglycollate-induced peritonitis, anti-Plg-R(KT) mAb markedly inhibited macrophage recruitment (by 58%), concomitant with a reduction in pro-MMP-9 activation in the inflamed peritoneum. Treatment with anti-Plg-R(KT) mAb did not further reduce the low level of macrophage recruitment in plasminogen-null mice. We conclude that Plg-R(KT) plays a key role in the plasminogen-dependent regulation of macrophage invasion, chemotactic migration, and recruitment in the inflammatory response.
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PMID:Regulation of macrophage migration by a novel plasminogen receptor Plg-R KT. 2194 Aug 22

Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular diseases, but the mechanism is unclear. The pathogenic risk of Lp(a) is associated with elevated plasma concentration, small isoforms of apolipoprotein [apo(a)], the unique apolipoprotein of Lp(a), and a mimic of plasminogen. Inflammation is associated with both the initiation and recovery of cardiovascular diseases, and plasminogen plays an important role in leukocyte recruitment. Because Lp(a)/apo(a) is expressed only in primates, transgenic mice were generated, apo(a)tg and Lp(a)tg mice, to determine whether Lp(a)/apo(a) modifies plasminogen-dependent leukocyte recruitment or whether apo(a) has an independent role in vivo. Plasminogen activation was markedly reduced in apo(a)tg and Lp(a)tg mice in both peritonitis and vascular injury inflammatory models, and was sufficient to reduce matrix metalloproteinase-9 activation and macrophage recruitment. Furthermore, neutrophil recruitment and the neutrophil cytokines, CXCL1/CXCL2, were suppressed in apo(a)tg mice in the abdominal aortic aneurysm model. Reconstitution of CXCL1 or CXCL2 restored neutrophil recruitment in apo(a)tg mice. Apo(a) in the plasminogen-deficient background and Lp(a)tg mice were resistant to inhibition of macrophage recruitment that was associated with an increased accumulation of apo(a) in the intimal layer of the vessel wall. These data indicate that, in inflammation, Lp(a)/apo(a) suppresses neutrophil recruitment by plasminogen-independent cytokine inhibition, and Lp(a)/apo(a) inhibits plasminogen activation and regulates matrix metalloproteinase-9 activation and macrophage recruitment.
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PMID:Lp(a)/apo(a) modulate MMP-9 activation and neutrophil cytokines in vivo in inflammation to regulate leukocyte recruitment. 2465 May 62


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