Transformation ofLeishmania mexicanametacyclic promastigotes to amastigote-like forms mediated by binding of human C-reactive protein

Infective metacyclic promastigote forms ofLeishmania mexicanaare introduced by the bite of sandfly vectors into their human hosts where they transform into the amastigote form. The kinetics of this process was examinedin vitroin response to different combinations of temperature (26 °C or 32 °C), pH (7.2 or 5.5), and exposure to human serum. Little transformation occurred at 26 °C/pH 7.2, intermediate levels at 26 °C/pH 5.5 and 32 °C/ pH 7.2, and the greatest response at 32 °C/pH 5.5. Transformation was stimulated by exposure to normal human serum, but was markedly reduced when serum previously incubated at 56 °C for 1 h was used (complement heat-inactivated). This stimulatory effect was reproduced by exposure to a single purified component of human serum, C-reactive protein (CRP). Binding of CRP to the whole surface ofL. mexicanametacyclic promastigotes, including the flagella, was demonstrated by an indirect fluorescent antibody test. The effect of purified CRP was dose dependent and occurred using normal serum concentrations. The stimulatory effect of whole serum was oblated by CRP depletion and restored by addition of purified CRP. The effects of cAMP analogues indicated that transformation could be mediated via an adenylate cyclase cascade.

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Altered platelet and coagulation function in moderate-to-severe COVID-19

Scientific Reports ◽

10.1038/s41598-021-95397-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rustem I. Litvinov ◽

Natalia G. Evtugina ◽

Alina D. Peshkova ◽

Svetlana I. Safiullina ◽

Izabella A. Andrianova ◽

...

Keyword(s):

Systemic Inflammation ◽

Blood Clot ◽

Immunosuppressive Drugs ◽

C Reactive Protein ◽

Reactive Protein ◽

Blood Clots ◽

Thrombotic Complications ◽

Hemostatic Disorders ◽

Kinetics Of

AbstractTo reveal if coagulopathies relate to the course of COVID-19, we examined 255 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about ¼ of cases were associated with high levels of C-reactive protein and antiphospholipid antibodies, which impeded coagulation in vitro. Contraction of blood clots was hindered in about ½ of patients, especially in severe and fatal cases, and correlated directly with prothrombotic parameters. A decrease in platelet contractility was due to moderate thrombocytopenia in combination with platelet dysfunction. Clots with impaired contraction were porous, had a low content of compressed polyhedral erythrocytes (polyhedrocytes) and an even distribution of fibrin, suggesting that the uncompacted intravital clots are more obstructive but patients could also be prone to bleeding. The absence of consumption coagulopathy suggests the predominance of local and/or regional microthrombosis rather than disseminated intravascular coagulation. The results obtained (i) confirm the importance of hemostatic disorders in COVID-19 and their relation to systemic inflammation; (ii) justify monitoring of hemostasis, including the kinetics of blood clot contraction; (iii) substantiate the active prophylaxis of thrombotic complications in COVID-19.

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High doses of intravenous immunoglobulin do not affect the recognition phase of the classical complement pathway

Blood ◽

10.1182/blood.v78.3.700.bloodjournal783700 ◽

1991 ◽

Vol 78 (3) ◽

pp. 700-702

Author(s):

M Basta ◽

LF Fries ◽

MM Frank

Keyword(s):

Human Serum ◽

Intravenous Immunoglobulin ◽

Normal Serum ◽

Normal Human Serum ◽

Complement Pathway ◽

Classical Complement Pathway ◽

Recognition Phase ◽

Normal Human ◽

Classical Complement

We have recently found that intravenous immunoglobulin (IVIg) prevents deposition of C3 and C4 fragments onto antibody sensitized erythrocytes. To find out if such an effect results from the blockade of the recognition phase of the classical complement cascade, we investigated the ability of human serum containing high concentrations of IVIg to deposit the recognition subunit of the first complement component (C1q) onto targets. Normal human serum supplemented in vitro with IVIg did not demonstrate reduced C1q binding to targets as determined by radiolabeled antihuman C1q antibody uptake. Similarly, methylamine-treated normal human serum to which IVIg was added was equally effective in terms of C1q binding as the same serum without IVIg. At increasing doses of sensitizing antibody, C1q uptake decreased proportionally; however, at all antibody dilution points C1q uptake was not significantly different in the serum with IVIg in comparison with normal serum. Serum from a patient treated with IVIg did not differ in its capacity to deposit C1q from the same patient's serum before therapy. Our data suggest that IVIg does not interfere with the recognition step of classical complement pathway. This is a US government work. There are no restrictions on its use.

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High doses of intravenous immunoglobulin do not affect the recognition phase of the classical complement pathway

Blood ◽

10.1182/blood.v78.3.700.700 ◽

1991 ◽

Vol 78 (3) ◽

pp. 700-702 ◽

Cited By ~ 16

Author(s):

M Basta ◽

LF Fries ◽

MM Frank

Keyword(s):

Human Serum ◽

Intravenous Immunoglobulin ◽

Normal Serum ◽

Normal Human Serum ◽

Complement Pathway ◽

Classical Complement Pathway ◽

Recognition Phase ◽

Normal Human ◽

Classical Complement

Abstract We have recently found that intravenous immunoglobulin (IVIg) prevents deposition of C3 and C4 fragments onto antibody sensitized erythrocytes. To find out if such an effect results from the blockade of the recognition phase of the classical complement cascade, we investigated the ability of human serum containing high concentrations of IVIg to deposit the recognition subunit of the first complement component (C1q) onto targets. Normal human serum supplemented in vitro with IVIg did not demonstrate reduced C1q binding to targets as determined by radiolabeled antihuman C1q antibody uptake. Similarly, methylamine-treated normal human serum to which IVIg was added was equally effective in terms of C1q binding as the same serum without IVIg. At increasing doses of sensitizing antibody, C1q uptake decreased proportionally; however, at all antibody dilution points C1q uptake was not significantly different in the serum with IVIg in comparison with normal serum. Serum from a patient treated with IVIg did not differ in its capacity to deposit C1q from the same patient's serum before therapy. Our data suggest that IVIg does not interfere with the recognition step of classical complement pathway. This is a US government work. There are no restrictions on its use.

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THE OCCURRENCE DURING ACUTE INFECTIONS OF A PROTEIN NOT NORMALLY PRESENT IN THE BLOOD

Journal of Experimental Medicine ◽

10.1084/jem.73.2.191 ◽

1941 ◽

Vol 73 (2) ◽

pp. 191-200 ◽

Cited By ~ 67

Author(s):

Colin M. MacLeod ◽

Oswald T. Avery

Keyword(s):

Human Serum ◽

Bacterial Infections ◽

Normal Human Serum ◽

C Reactive Protein ◽

Reactive Protein ◽

Acute Infections ◽

Immunological Specificity ◽

Normal Human ◽

Immunological Reactions ◽

Acute Bacterial Infections

The C-reactive protein present in the albumin fraction of the serum of patients during certain acute bacterial infections is highly antigenic upon injection into rabbits. The antiserum thus prepared reacts specifically with this protein and does not react with the proteins of normal human serum. Immunological specificity has been demonstrated by both precipitin and complement-fixation tests. Antiserum prepared in rabbits to the C-reactive protein from human sources also reacts specifically with the similar protein in the serum of monkeys acutely ill with experimental pneumococcus infection. By means of immunological reactions it is possible to detect amounts of reactive protein which are too small to yield a visible precipitate in tests with the C polysaccharide. Certain of the properties are discussed which distinguish the C-reactive protein from the proteins of normal human serum.

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A panel of eight tests in the serodiagnosis and immunological evaluation of acute brucellosis

Eastern Mediterranean Health Journal ◽

10.26719/2000.6.2-3.304 ◽

2000 ◽

Vol 6 (2-3) ◽

pp. 304-312

Author(s):

W. A. Dabdoob ◽

Z. A. Abdulla

Keyword(s):

Indirect Fluorescent Antibody Test ◽

Fluorescent Antibody ◽

Antibody Test ◽

Control Group ◽

Normal Numbers ◽

C Reactive Protein ◽

Reactive Protein ◽

The Rose ◽

Immunological Evaluation ◽

Apparently Healthy

A panel of eight tests was used to study 200 cases of acute brucellosis, 200 patients negative for brucella as a control group and 200 apparently healthy individuals as a second control group. The best diagnostic test was the rose Bengal test using an imported reagent [BioMerieux, France] and 2 local reagents. This test was improved from being a screening test to be a titrable one. The best two tests used together were the tube agglutination test with Coomb-like test. The indirect fluorescent antibody test had no advantages over the use of other tests. The 2-mercaptoethanol test and C-reactive protein test were useful in checking the brucellosis activity. Normal numbers of E-rosette forming cells and inefficient neutrophils in phagocytosis were found in peripheral blood during acute brucellosis

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Interactions of C-reactive protein with the complement system. III. Complement-dependent passive hemolysis initiated by CRP.

Journal of Experimental Medicine ◽

10.1084/jem.142.5.1065 ◽

1975 ◽

Vol 142 (5) ◽

pp. 1065-1077 ◽

Cited By ~ 80

Author(s):

A.P. Osmand ◽

R.F. Mortensen ◽

Joan Siegel ◽

H. Gewurz

Keyword(s):

Guinea Pig ◽

Human Serum ◽

Complete System ◽

Gel Filtration ◽

C Reactive Protein ◽

Inflammatory Reactions ◽

Reactive Protein ◽

Rabbit Igg ◽

The Complement System ◽

Pig Serum

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.

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The influence of sugar–protein complexes on the thermostability of C-reactive protein (CRP)

Scientific Reports ◽

10.1038/s41598-021-92522-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Andreea Lorena Mateescu ◽

Nicolae-Bogdan Mincu ◽

Silvana Vasilca ◽

Roxana Apetrei ◽

Diana Stan ◽

...

Keyword(s):

Diagnostic Tests ◽

Protein Complexes ◽

C Reactive Protein ◽

Time Resolved Fluorescence ◽

Time Resolved ◽

Reactive Protein ◽

In Vitro Diagnostic ◽

The Stability ◽

Positive Controls

AbstractThe purpose of the present study was to evaluate de influence of protein–sugar complexation on the stability and functionality of C-reactive protein, after exposure to constant high temperatures, in order to develop highly stable positive controls for in-vitro diagnostic tests. C-reactive protein is a plasmatic protein used as a biomarker for the diagnosis of a series of health problems such as ulcerative colitis, cardiovascular diseases, metabolic syndrome, due to its essential role in the evolution of chronic inflammation. The sugar–protein interaction was investigated using steady state and time resolved fluorescence. The results revealed that there are more than two classes of tryptophan, with different degree of accessibility for the quencher molecule. Our study also revealed that sugar–protein complexes have superior thermostability, especially after gamma irradiation at 2 kGy, the protein being stable and functional even after 22 days exposure to 40 °C.

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Low density lipoprotein and very low density lipoprotein are selectively bound by aggregated C-reactive protein.

Journal of Experimental Medicine ◽

10.1084/jem.156.1.230 ◽

1982 ◽

Vol 156 (1) ◽

pp. 230-242 ◽

Cited By ~ 120

Author(s):

F C de Beer ◽

A K Soutar ◽

M L Baltz ◽

I M Trayner ◽

A Feinstein ◽

...

Keyword(s):

Acute Phase ◽

Solid Phase ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Very Low Density Lipoprotein ◽

Low Density ◽

C Reactive Protein ◽

Calcium Dependent ◽

Reactive Protein

C-reactive protein (CRP), the classical acute-phase protein, can bind phospholipids by virtue of its specific, calcium-dependent reactivity with phosphorylcholine residues. However, analysis of acute-phase serum by gel filtration and by density gradient ultracentrifugation showed that the CRP was in a free, uncomplexed form, despite the coexistent presence of the various classes of serum lipoproteins, all of which contain phospholipids. In contrast, when isolated CRP was aggregated by immobilization at a sufficient density on a solid phase and then exposed to normal human serum, it selectively bound low density lipoprotein (LDL) and traces of very low density lipoprotein. The reaction was calcium dependent and reversible by free phosphorylcholine but not by heparin. LDL isolated from normal plasma was also bound by aggregated CRP. CRP reacts in vitro with a wide variety of different ligands both of extrinsic and of autogenous origin, e.g., microbial products and damaged cell membranes, respectively. If CRP aggregated in vivo by complexing with these ligands than acquires the capacity to selectively bind LDL, the phenomenon may have significant implications for the function of CRP and for the metabolism, clearance, and deposition of LDL.

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Post-operative kinetics of C-reactive protein to distinguish between bacterial infection and systemic inflammation in infants after cardiopulmonary bypass surgery: the early and the late period

Cardiology in the Young ◽

10.1017/s1047951121003231 ◽

2021 ◽

pp. 1-8

Author(s):

Hanna Renk ◽

David Grosse ◽

Sarah Schober ◽

Christian Schlensak ◽

Michael Hofbeck ◽

...

Keyword(s):

Cardiopulmonary Bypass ◽

Bacterial Infection ◽

Congenital Heart ◽

Bypass Surgery ◽

Heart Surgery ◽

Congenital Heart Surgery ◽

C Reactive Protein ◽

Reactive Protein ◽

Post Operative Period ◽

Kinetics Of

Abstract Objectives: Differentiation between post-operative inflammation and bacterial infection remains an important issue in infants following congenital heart surgery. We primarily assessed kinetics and predictive value of C-reactive protein for bacterial infection in the early (days 0–4) and late (days 5–28) period after cardiopulmonary bypass surgery. Secondary objectives were frequency, type, and timing of post-operative infection related to the risk adjustment for congenital heart surgery score. Methods: This 3-year single-centre retrospective cohort study in a paediatric cardiac ICU analysed 191 infants accounting for 235 episodes of CPBP surgery. Primary outcome was kinetics of CRP in the first 28 days after CPBP surgery in infected and non-infected patients. Results: We observed 22 infectious episodes in the early and 34 in the late post-operative period. CRP kinetics in the early post-operative period did not accurately differentiate between infected and non-infected patients. In the late post-operative period, infected infants displayed significantly higher CRP values with a median of 7.91 (1.64–22.02) and 6.92 mg/dl (1.92–19.65) on days 2 and 3 compared to 4.02 (1.99–15.9) and 3.72 mg/dl (1.08–9.72) in the non-infection group. Combining CRP on days 2 and 3 after suspicion of infection revealed a cut-off of 9.47 mg/L with an acceptable predictive accuracy of 76%. Conclusions: In neonates and infants, CRP kinetics is not useful to predict infection in the first 72 hours after CPBP surgery due to the inflammatory response. However, in the late post-operative period, CRP is a valuable adjunctive diagnostic test in conjunction with clinical presentation and microbiological diagnostics.

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