Rat C-reactive protein can activate the complement system

2001 ◽  
Vol 1 (S2) ◽  
Author(s):  
Niubel Diaz-Padilla ◽  
Wim KBleeker ◽  
C Erik Hack
Author(s):  
Thona Wusu

Introduction: Schizophrenia is a severe mental disorder among nationalities of the world, which has a substantial social and economic effect. Scientific therapeutic drugs have proved abortive due to adverse effects. Aim: The study investigated the repression of the complement system by aqueous extract of alligator pepper on schizophrenia. Methods: Male mice were induced with schizophrenia using ketamine and dexamethasone; the mice were treated with aqueous extract of alligator pepper (200mg/ml and 400mg/ml) respectively for ten days. After which their brain was removed, and analysed for dopamine. Blood samples was collected from the animal and plasma was used to determine the level of complement component (3 and 4), and C-reactive protein spectrophotometrically. Phytochemical content of the aqueous extract was also done spectrophotometrically, and characterization was confirmed using FTIR. Result: The alligator plant extract constituent includes flavonoids, tannins, saponin, steroids, phlabotannis, terpenoids, and cardiac glycoside. With a tannins having a concentration of 1292.6 µg/ml and 726.8µg/ml, phenol had a concentration of 221.7 µg/ml and 94.2 µg/ml and flavonoids had a concentration of 105.3 µg/ml and 100.0 µg/ml at 200mg/ml and 400mg/ml plant concentration respectively. The alligator pepper reversed the effect of ketamine and dexamethasone induced schizophrenia by decreasing the level of C-reactive protein , complement component (3 and 4) and dopamine significantly (<0.0001) in a dose dependent manner, in all the groups compared to the control. Conclusion: The high phenolic and flavonoids content in alligator pepper may be responsible for the antipsychotic property of alligator pepper. Thus, probable natural therapy for schizophrenia.


2020 ◽  
pp. 30-34
Author(s):  
V. V. Boyko ◽  
D. O. Yevtushenko ◽  
I. V. Kryvorotko ◽  
I. A. Taraban ◽  
D. V. Minukhin ◽  
...  

Summary. The etiology of the development of adhesive disease — the most common postoperative complication — can be determined by epigenomic disorders related to various links of resistance and immunogenetic control. Purpose of the study. To study the epigenomic factors in the development of adhesive disease, the immune status of patients operated on in the abdominal cavity was studied. The comparison group included 55 patients with a complicated course of peritoneal commissural disease, the main group consisted of 59 patients operated on on the abdominal organs on the background of peritoneal commissural disease, the course of which was asymptomatic. Results and its discussion. The revealed epigenomic factors associated with the risk of developing adhesive disease: belongs to an increase in the concentration of acute phase proteins - ceruloplasmin, haptoglobin, C-reactive protein, C3 fragment of the complement system proteins, changes in the expression of adhesion molecule genes (CD31 increased by 10 %, CD54 increased to 24.1 % in comparison with the comparison group — 13.25 %). Conclusions. The results of our studies showed that patients with adhesive disease have a wide range of epigenome trigger factors. Epigenomic factors associated with the risk of developing adhesive disease include an increase in the concentration of acute phase proteins - ceruloplasmin, haptoglobin, C-reactive protein, C3 fragment of the complement system proteins, changes in the expression of adhesion molecule genes (CD31 increased by 10 %, CD54 increased to 24, 1 % compared with the comparison group - 13.25 %)


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Oliver Zimmermann ◽  
Dimitar E Manolov ◽  
Ziya Kaya ◽  
Thomas P Zwaka ◽  
Magdalena Bienek-Ziolkowski ◽  
...  

Background: C-reactive protein (CRP) has been suggested as a risk factor in cardiovascular disease. Recently, it has been shown that CRP binds to ligands exposed in ischaemic damaged tissue and activates the complement system. Furthermore, CRP was demonstrated to be strongly and independently associated with the occurrence of heart failure in men. In this study we have investigated the presence of CRP and the Terminal Complement Complex (C5b-9) in the myocardium of patients suffering from non-ischaemic heart failure. Methods and Results: Endomyocardial biopsies were taken from 151 patients suffering from dilated cardiomyopathy. Biopsies were immunohistochemically analysed for the presence and distribution pattern of CRP and C5b-9. In 39 patients plasma levels of hsCRP and NT-proBNP were measured and correlated with myocardial biopsy findings. In 47 patients a positive staining for CRP and in 141 patients a positive staining for C5b-9 was detected. CRP and C5b-9 significantly co-localised within the myocardium. A negative correlation was observed for plasma hsCRP levels and myocardial CRP. Conclusions: This study shows for the first time that CRP is frequently present in the myocardium of patients suffering from non-ischaemic dilated cardiomyopathy and co-localises with the Terminal Complement Complex. CRP may contribute to myocardial damage in dilated cardiomyopathy via activating the complement system.


1975 ◽  
Vol 142 (5) ◽  
pp. 1065-1077 ◽  
Author(s):  
A.P. Osmand ◽  
R.F. Mortensen ◽  
Joan Siegel ◽  
H. Gewurz

Interactions of CRP with various substrates in the presence of human serum have been shown to result in efficient activation of C components C1-C5. We now report the ability of CRP to initiate C-dependent hemolysis. For this purpose CRP was isolated by affinity chromatography using pneumococcal CPS and gel filtration; its purity was established by several criteria. Erythrocytes were coated with CPS (E-CPS) and passively sensitized with CRP. C-dependent lysis of these cells was observed upon the addition of suitably absorbed human serum, and the efficiency of hemolysis compared favorably with that initiated by rabbit IgG anti-CPS antibody. CRP also sensitized E-CPS for lysis by guinea pig C; partial lysis was seen when C4-deficient guinea pig serum was used, suggesting that CRP also shares with antibody the ability of CRP to fully activate the C system and provide further evidence for a role for CRP similar to that of antibody in the initiation and modulation of inflammatory reactions via the complete system.


2021 ◽  
Vol 23 (4) ◽  
pp. 927-932
Author(s):  
O. B.J. Po ◽  
A. A. Konoplya ◽  
I. N. Medvedeva

The study aimed to compare the effectiveness of various pharmacotherapy regimens for infertility of tubo-peritoneal genesis. Under constant supervision were 96 patients referred to the hospital for diagnostic laparoscopy for infertility of tubo-peritoneal genesis, divided equally into 4 groups depending on the pharmacological treatment methods: the 1st group received basic pharmacotherapy (BPT) after endoscopic surgery (antibacterial, antifungal, vitamin therapy). Patients of groups 2-4, in addition to BPT, received Hepon, Cycloferon or Lavomax, respectively. The control group consisted of 38 gynecologically healthy women. Laboratory examination was performed within 24 hours after the operation and on the 30th day after BPT. Vaginocervical lavage and plasma were assayed for the activity of lipid peroxidation processes, the state of the antioxidant system, the level of stable nitric oxide metabolites, neopterin, C-reactive protein, cytokines (TNFα, IL-1β, IL-8, IFNγ, IL-18, G-CSF, IL-4, IL-10), immunoglobulins (IgM, IgG, IgA, sIgA), components of the complement system (C3, C4, C5, C5А), phagocytic and oxygen-dependent activity of polymorphonuclear leukocytes. It was established that the use of immunomodulatory and antiviral activity medication with BPT according to the degree of increasing efficiency in the correction of immunometabolic laboratory parameters at the systemic and local level in infertility of tuboperitoneal genesis is as the following sequence: basic pharmacotherapy < basic pharmacotherapy + Hepon < basic pharmacotherapy + Cycloferon < basic pharmacotherapy + Lavomax. 


1975 ◽  
Vol 142 (3) ◽  
pp. 709-721 ◽  
Author(s):  
J Siegel ◽  
A P Osmand ◽  
M F Wilson ◽  
H Gewurz

Cationic homopolymers of poly-L-lysine were found to activate complement (C) via C-reactive protein (CRP) and deplete C3 and C5 as well as early-acting C components. Maximum C consumption was obtained with polymers of 2,000-8,000 daltons; polymers of 1,700, 11,000, and 23,000 daltons were intermediate in reactivity, while L-lysine, lysyl-L-lysine, tetra-L-lysine, and polymers of 70,000-400,000 daltons lacked significant C-consuming activity. Naturally occurring polycations which consumed C in the presence of CRP included myelin basic proteins, cationic proteins of rabbit leukocytes, and both lysine- and arginine-rich histones; poly-L-arginine polymers of 17,000 but not 65,000 daltons also were C-consuming. Polycations without such reactivity included poly-L-orithine (5,000 and 165,000 daltons), egg white and human lysozymes, and Polybrene. The polycations which failed to induce C consumption via CRP, inhibited its consumption by both active polycations and by C-polysaccharide (CPS). The relative inhibitory capacity of phosphorylcholine and polycations in CPS- and polycations-CRP systems was consistent with the concept that phosphate esters and polycations react at the same or an overlapping combining site. The ability of certain polycations to activate C via CRP increases the potential for initiation of host reactions via C. The capacity of other polycations to inhibit C activation via CRP introduces a potential for physiologic or pharmacologic manipulation. These considerations would seem to expand the potential role of CRP in the initiation and modulation of the inflammatory response.


1993 ◽  
Vol 21 (1) ◽  
pp. 50-55 ◽  
Author(s):  
M. Tulunay ◽  
S. Demiralp ◽  
S. Tastan ◽  
H. Akalin ◽  
U. Ozyurda ◽  
...  

Complement activation has been deemed responsible for the damaging effects of cardiopulmonary bypass (CPB) in patients undergoing open heart surgery. We studied C3, C4 and C-reactive protein (CRP) in 22 patients undergoing CPB. In Group 1 (11 patients), protamine was given intravenously and in Group 2 (11 patients), via the aortic root after CPB. Significant decreases were observed in C3 and C4 during CPB in both groups indicating complement activation primarily by the classic pathway. Protamine did not lead to further activation of the complement system. In both groups, C3 levels gradually returned toward baseline within 24 hours but C4 levels were still lower than baseline 24 hours postoperatively. CPB and protamine administration did not cause any significant changes in CRP levels, but CRP increased abruptly 24 hours after operation. Although activation of complement system during CPB is expected to invoke an acute phase response, we conclude that this period is not long enough to induce an increased production of CRP in response to tissue injury or inflammation.


Immunology ◽  
2003 ◽  
Vol 109 (4) ◽  
pp. 564-571 ◽  
Author(s):  
Niubel Diaz Padilla ◽  
Wim K. Bleeker ◽  
Yvonne Lubbers ◽  
Gemma M. M. Rigter ◽  
Gerard J. van Mierlo ◽  
...  

1974 ◽  
Vol 140 (3) ◽  
pp. 631-647 ◽  
Author(s):  
Joan Siegel ◽  
Rosemarie Rent ◽  
Henry Gewurz

Protamine sulfate was found to consume large amounts of C selectively during preincubation with sera of individuals in the "acute phase". Marked depletion of C1, C4, and C2 with minimal, if any, depletion of C3-9, was observed. The consumption was time and temperature dependent, occurring most rapidly and extensively at 37°C, 0.10 M relative salt concentration and pH 7.5–8.0; it required calcium ions. It was mediated by a heat-stable nondialyzable factor which separated with C-reactive protein (CRP) during fractionation and purification, correlated with serum CRP levels, and, like other known reactivities of CRP, was inhibited by phosphoryl choline. Preparations of CRP purified either from serum or ascites resulted in consumption of large amounts of C1, C4, and C2 when preincubated with normal serum and protamine. We conclude that CRP is a potent activator of the C system at the level of C1, and that polycations such as protamine sulfate are substrates of CRP which can bring about this activation. It seems not unlikely that one role of CRP in health and disease involves its ability to interact with the C system.


2021 ◽  
Vol 12 ◽  
Author(s):  
Dylan P. Noone ◽  
Tijn T. van der Velden ◽  
Thomas H. Sharp

The pentraxin family of proteins includes C-reactive protein (CRP), a canonical marker for the acute phase inflammatory response. As compared to normal physiological conditions in human serum, under conditions associated with damage and inflammation, such as acidosis and the oxidative burst, CRP exhibits modulated biochemical properties that may have a structural basis. Here, we explore how pH and ligand binding affect the structure and biochemical properties of CRP. Cryo-electron microscopy was used to solve structures of CRP at pH 7.5 or pH 5 and in the presence or absence of the ligand phosphocholine (PCh), which yielded 7 new high-resolution structures of CRP, including pentameric and decameric complexes. Structures previously derived from crystallography were imperfect pentagons, as shown by the variable angles between each subunit, whereas pentameric CRP derived from cryoEM was found to have C5 symmetry, with subunits forming a regular pentagon with equal angles. This discrepancy indicates flexibility at the interfaces of monomers that may relate to activation of the complement system by the C1 complex. CRP also appears to readily decamerise in solution into dimers of pentamers, which obscures the postulated binding sites for C1. Subtle structural rearrangements were observed between the conditions tested, including a putative change in histidine protonation that may prime the disulphide bridges for reduction and enhanced ability to activate the immune system. Enzyme-linked immunosorbent assays showed that CRP had markedly increased association to the C1 complex and immunoglobulins under conditions associated with acidosis, whilst a reduction in the Ca2+ concentration lowered this pH-sensitivity for C1q, but not immunoglobulins, suggesting different modes of binding. These data suggest a model whereby a change in the ionic nature of CRP and immunological proteins can make it more adhesive to potential ligands without large structural rearrangements.


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