scholarly journals Fibrinolysis: A Primordial System Linked to the Immune Response

2021 ◽  
Vol 22 (7) ◽  
pp. 3406
Author(s):  
Robert L. Medcalf ◽  
Charithani B. Keragala

The fibrinolytic system provides an essential means to remove fibrin deposits and blood clots. The actual protease responsible for this is plasmin, formed from its precursor, plasminogen. Fibrin is heralded as it most renowned substrate but for many years plasmin has been known to cleave many other substrates, and to also activate other proteolytic systems. Recent clinical studies have shown that the promotion of plasmin can lead to an immunosuppressed phenotype, in part via its ability to modulate cytokine expression. Almost all immune cells harbor at least one of a dozen plasminogen receptors that allows plasmin formation on the cell surface that in turn modulates immune cell behavior. Similarly, a multitude of pathogens can also express their own plasminogen activators, or contain surface proteins that provide binding sites host plasminogen. Plasmin formed under these circumstances also empowers these pathogens to modulate host immune defense mechanisms. Phylogenetic studies have revealed that the plasminogen activating system predates the appearance of fibrin, indicating that plasmin did not evolve as a fibrinolytic protease but perhaps has its roots as an immune modifying protease. While its fibrin removing capacity became apparent in lower vertebrates these primitive under-appreciated immune modifying functions still remain and are now becoming more recognised.

Tick-borne encephalitis virus (TBEV) exists in natural foci, which are areas where TBEV is circulating among its vectors (ticks of different species and genera) and reservoir hosts (usually rodents and small mammals). Based on phylogenetic studies, four TBEV subtypes (Far-Eastern, Siberian, European, Baikalian) and two putative subtypes (Himalayan and “178-79” group) are known. Within each subtype, some genetic lineages are described. The European subtype (TBEV-EU) (formerly known also as the “Western subtype”) of TBEV is prevalent in Europe, but it was also isolated in Western and Eastern Siberia in Russia and South Korea. The Far-Eastern subtype (TBEV-FE) was preferably found in the territory of the far-eastern part of Eurasia, but some strains were isolated in other regions of Eurasia. The Siberian (TBEV-SIB) subtype is the most common and has been found in almost all TBEV habitat areas. The Baikalian subtype is prevalent around Lake Baikal and was isolated several times from ticks and rodents. In addition to the four TBEV subtypes, one single isolate of TBEV (178-79) and two genetic sequences (Himalayan) supposed to be new TBEV subtypes were described in Eastern Siberia and China. The data on TBEV seroprevalence in humans and animals can serve as an indication for the presence or absence of TBEV in studied area.


1986 ◽  
Vol 108 (2) ◽  
pp. 267-273 ◽  
Author(s):  
S. Kyakumoto ◽  
R. Kurokawa ◽  
Y. Ohara-Nemoto ◽  
M. Ota

ABSTRACT Cytosol and nuclear androgen receptors in submandibular glands of male and female mice were measured by an exchange assay at 0 °C. The binding of [3H]methyltrienolone to cytosol receptors in females was mostly saturated within a short period of incubation (3 h), whereas the saturation was much slower in males; suggesting that almost all of the cytosol receptors were unoccupied in females and the receptors were partially occupied in males. Nuclear receptors were extracted with pyridoxal 5′-phosphate (5 mmol/l) from nuclear fractions with 93–95% efficiency. The exchange of the bound steroids occurred by 24–48 h at 0 °C, suggesting that most of the nuclear androgen receptor was occupied. The binding was low at higher temperatures, probably due to inactivation of the receptor. Scatchard analysis showed that the apparent dissociation constants of cytosol and nuclear receptors were similar (0·8 and 0·9 nmol/l respectively) in both sexes. On the other hand, the number of androgen-binding sites in the nucleus was much higher in males than in females (1052 fmol/mg DNA and 32 fmol/mg DNA respectively), while the number in the cytosol was higher in females than in males (512 fmol/mg DNA and 368 fmol/mg DNA respectively). These observations show that androgen receptors exist mainly (74%) in the nuclei of males, while they exist mostly (94%) in the cytosol of females. J. Endocr. (1986) 108, 267–273


2021 ◽  
Author(s):  
Yingrou Tan ◽  
Hong Liang Tey ◽  
Shu Zhen Chong ◽  
Lai Guan Ng

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1832-1844 ◽  
Author(s):  
J. Annelies E. Polman ◽  
E. Ronald de Kloet ◽  
Nicole A. Datson

Abstract In the present study, genomic binding sites of glucocorticoid receptors (GR) were identified in vivo in the rat hippocampus applying chromatin immunoprecipitation followed by next-generation sequencing. We identified 2470 significant GR-binding sites (GBS) and were able to confirm GR binding to a random selection of these GBS covering a wide range of P values. Analysis of the genomic distribution of the significant GBS revealed a high prevalence of intragenic GBS. Gene ontology clusters involved in neuronal plasticity and other essential neuronal processes were overrepresented among the genes harboring a GBS or located in the vicinity of a GBS. Male adrenalectomized rats were challenged with increasing doses of the GR agonist corticosterone (CORT) ranging from 3 to 3000 μg/kg, resulting in clear differences in the GR-binding profile to individual GBS. Two groups of GBS could be distinguished: a low-CORT group that displayed GR binding across the full range of CORT concentrations, and a second high-CORT group that displayed significant GR binding only after administering the highest concentration of CORT. All validated GBS, in both the low-CORT and high-CORT groups, displayed mineralocorticoid receptor binding, which remained relatively constant from 30 μg/kg CORT upward. Motif analysis revealed that almost all GBS contained a glucocorticoid response element resembling the consensus motif in literature. In addition, motifs corresponding with new potential GR-interacting proteins were identified, such as zinc finger and BTB domain containing 3 (Zbtb3) and CUP (CG11181 gene product from transcript CG11181-RB), which may be involved in GR-dependent transactivation and transrepression, respectively. In conclusion, our results highlight the existence of 2 populations of GBS in the rat hippocampal genome.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yin-Fu Sun ◽  
Jiang Pi ◽  
Jun-Fa Xu

Exosomes are cell-derived nanovesicles carrying protein, lipid, and nucleic acid for secreting cells, and act as significant signal transport vectors for cell-cell communication and immune modulation. Immune-cell-derived exosomes have been found to contain molecules involved in immunological pathways, such as MHCII, cytokines, and pathogenic antigens. Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most fatal infectious diseases. The pathogen for tuberculosis escapes the immune defense and continues to replicate despite rigorous and complicate host cell mechanisms. The infected-cell-derived exosomes under this circumstance are found to trigger different immune responses, such as inflammation, antigen presentation, and activate subsequent pathways, highlighting the critical role of exosomes in anti-MTB immune response. Additionally, as a novel kind of delivery system, exosomes show potential in developing new vaccination and treatment of tuberculosis. We here summarize recent research progress regarding exosomes in the immune environment during MTB infection, and further discuss the potential of exosomes as delivery system for novel anti-MTB vaccines and therapies.


1978 ◽  
Vol 57 (4) ◽  
pp. 625-630 ◽  
Author(s):  
Martin Marshack ◽  
Patrick Toto ◽  
Ronald Kerman

Immune stimulation with an agent such as dinitrochlorobenzene (DNCB) may delay chemcal carcinogenesis. Dimethylbenzanthracene (DMBA) was used to chemically induce tumors in the hamster buccal pouch. Hamsters were studied for the effect of DNCB sensitization in the buccal pouch prior to or after DMBA tumor induction. At appropriate time intervals the hamsters were sacrificed and each cheek pouch was examined histologically for the development of DMBA-induced tumors and for the presence of lymphoid cells infiltrating the tumor site. The results show that DNCB immunotherapy or immunoprophylaxis prior to or following DMBA tumor induction can alter the type of tumor produced and stimulate an infiltration of lymphoid cells into the tumor area probably invoking immune defense mechanisms.


2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Maarten F. de Jong ◽  
Neal M. Alto

ABSTRACT The enteric attaching and effacing (A/E) pathogens enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) and the invasive pathogens enteroinvasive E. coli (EIEC) and Shigella encode type III secretion systems (T3SS) used to inject effector proteins into human host cells during infection. Among these are a group of effectors required for NF-κB-mediated host immune evasion. Recent studies have identified several effector proteins from A/E pathogens and EIEC/ Shigella that are involved in suppression of NF-κB and have uncovered their cellular and molecular functions. A novel mechanism among these effectors from both groups of pathogens is to coordinate effector function during infection. This cooperativity among effector proteins explains how bacterial pathogens are able to effectively suppress innate immune defense mechanisms in response to diverse classes of immune receptor signaling complexes (RSCs) stimulated during infection.


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