Phase Protein Alpha 1-acid Glycoprotein Research Articles

Lung Protection After Severe Thermal Burns With Adenosine, Lidocaine, and Magnesium (ALM) Resuscitation and Importance of Shams in a Rat Model.

The management of severe burns remains a complex challenge. Adenosine, lidocaine, and magnesium (ALM) resuscitation therapy has been shown to protect against hemorrhagic shock and traumatic injury. The aim of the present study was to investigate the early protective effects of small-volume ALM fluid resuscitation in a rat model of 30% total body surface area (TBSA) thermal injury. Male Sprague-Dawley rats (320-340 g; n = 25) were randomly assigned to: 1) Sham (surgical instrumentation and saline infusion, without burn, n = 5), 2) Saline resuscitation group (n = 10), or 3) ALM resuscitation group (n = 10). Treatments were initiated 15-min after burn trauma, including 0.7 mL/kg 3% NaCl ± ALM bolus and 0.25-0.5 mL/kg/h 0.9% NaCl ± ALM drip, with animals monitored to 8.25-hr post-burn. Hemodynamics, cardiac function, blood chemistry, hematology, endothelial injury markers and histopathology were assessed. Survival was 100% for Shams and 90% for both ALM and Saline groups. Shams underwent significant physiological, immune and hematological changes over time as a result of surgical traums. ALM significantly reduced malondialdehyde levels in the lungs compared to Saline (P = .023), and showed minimal alveolar destruction and inflammatory cell infiltration (P < .001). ALM also improved cardiac function and oxygen delivery (21%, P = .418 vs Saline), reduced gut injury (P < .001 vs Saline), and increased plasma adiponectin (P < .001 vs baseline). Circulating levels of the acute phase protein alpha 1-acid glycoprotein (AGP) increased 1.6-times (P < .001), which may have impacted ALM's therapeutic efficacy. We conclude that small-volume ALM therapy significantly reduced lung oxidative stress and preserved alveolar integrity following severe burn trauma. Further studies are required to assess higher ALM doses with longer monitoring periods.

Alpha-1 Acid Glycoprotein Reduction Differentiated Recovery from Remission in a Small Cohort of Cats Treated for Feline Infectious Peritonitis.

Feline infectious peritonitis (FIP) is a systemic immune-mediated inflammatory perivasculitis that occurs in a minority of cats infected with feline coronavirus (FCoV). Various therapies have been employed to treat this condition, which was previously usually fatal, though no parameters for differentiating FIP recovery from remission have been defined to enable clinicians to decide when it is safe to discontinue treatment. This retrospective observational study shows that a consistent reduction of the acute phase protein alpha-1 acid glycoprotein (AGP) to within normal limits (WNL, i.e., 500 μg/mL or below), as opposed to duration of survival, distinguishes recovery from remission. Forty-two cats were diagnosed with FIP: 75% (12/16) of effusive and 54% (14/26) of non-effusive FIP cases recovered. Presenting with the effusive or non-effusive form did not affect whether or not a cat fully recovered (p = 0.2). AGP consistently reduced to WNL in 26 recovered cats but remained elevated in 16 cats in remission, dipping to normal once in two of the latter. Anaemia was present in 77% (23/30) of the cats and resolved more quickly than AGP in six recovered cats. The presence of anaemia did not affect the cat’s chances of recovery (p = 0.1). Lymphopenia was observed in 43% (16/37) of the cats and reversed in nine recovered cats but did not reverse in seven lymphopenic cats in the remission group. Fewer recovered cats (9/24: 37%) than remission cats (7/13: 54%) were lymphopenic, but the difference was not statistically different (p = 0.5). Hyperglobulinaemia was slower than AGP to return to WNL in the recovered cats. FCoV antibody titre was high in all 42 cats at the outset. It decreased significantly in 7 recovered cats but too slowly to be a useful parameter to determine discontinuation of antiviral treatments. Conclusion: a sustained return to normal levels of AGP was the most rapid and consistent indicator for differentiating recovery from remission following treatment for FIP. This study provides a useful model for differentiating recovery from chronic coronavirus disease using acute phase protein monitoring.

On the binding reaction of loratadine with human serum acute phase protein alpha 1-acid glycoprotein

Loratadine is an important anti-allergic drug. It is a second generation antihistamine drug used to treat allergic rhinitis, hay fever and urticaria. Human serum alpha 1-acid glycoprotein (AG) is an important acute phase protein and its serum concentration is found to increase in inflammation and acute response.The binding interaction between loratadine and AG is studied using spectroscopy and molecular docking techniques. The results obtained from fluorescence quenching experiments demonstrated that the fluorescence intensity of AG is quenched by loratadine. Loratadine was found to bind AG with the binding constant of ≈104 at 298 K. The Gibb’s free energy change was found to be negative for the interaction of loratadine with AG indicating the binding process is spontaneous. Binding of loratadine with AG induced ordered structures in the protein. Hydrogen bonding and hydrophobic interactions were the main bonding forces between AG–loratadine as revealed by molecular docking results. This study suggests the importance of binding of anti-allergic drug to AG spatially in the diseases where the plasma concentration of AG increases many folds and interaction with this protein becomes significant. This study will help in design of drug dosage and adjustment accordingly to achieve optimal treatment outcome. Communicated by Ramaswamy H. Sarma

A pilot study to evaluate the serum Alpha-1 acid glycoprotein response in cats suffering from feline chronic gingivostomatitis

BackgroundFeline chronic gingivostomatitis (FCGS) is a multifactorial immune-mediated disease that can lead to chronic pain, anorexia, and weight loss and has substantial health and welfare effects. Currently, the recommended treatment includes dental extractions to decrease the inflammatory stimulation associated with dental plaque. However, complete remission is observed in less than half of the cases, and the majority need comprehensive medical management. This study aimed to evaluate the serum levels of the acute phase protein alpha-1 acid glycoprotein (AGP) in cats with FCGS and to examine whether dental extractions contribute to a significant decrease in the systemic inflammatory response at two postoperative time points.ResultsAGP serum concentrations in the cats with FCGS were significantly higher at all time points than that in the control groups and were significantly correlated with the global caudal stomatitis score at day 0 but not at day 30 or 60. A significant improvement of some clinical scores, such as perceived comfort and global caudal stomatitis, was observed 60 days after the dental extraction. However, the levels of AGP did not significantly change over time.ConclusionsCats with FCGS were more likely to have a systemic inflammatory response compared with age- and dental disease-matched controls. Dental extractions, in most cases, did not contribute to a significant decrease of AGP both at 30 and 60 days. Therefore, this study reinforces the need to pursue comprehensive medical management after dental extractions to attenuate the systemic inflammatory response as a result of this disease.

The bovine acute phase protein α1-acid glycoprotein (AGP) can disrupt Staphylococcus aureus biofilm

Staphylococcus aureus biofilm-related infections are of clinical concern due to the capability of bacterial colonies to adapt to a hostile environment. The present study investigated the capability of the acute phase protein alpha 1-acid glycoprotein (AGP) to a) disrupt already established S. aureus biofilm and b) interfere with the biofilm de novo production by using Microtiter Plate assay (MtP) on field strains isolated from infected quarters by assessing. The present study also investigated whether AGP could interfere with the expression of bacterial genes related to biofilm formation (icaA, icaD, icaB, and icaC) and adhesive virulence determinants (fnbA, fnbB, clfA, clfB, fib, ebps, eno) by quantitative real-time PCR (qPCR). The results provided the evidence that AGP could disrupt the biofilm structure only when it was already developed, but could not prevent the de novo biofilm formation. Moreover, AGP could interfere with the expression levels of genes involved in biofilm formation in a dose- and strain-dependent way, by upregulating, or downregulating, icaABC genes and fnbB, respectively. The results presented in this study provide new insights about the direct antibacterial activity of AGP in bovine milk. It remains to be demonstrated the molecular bases of AGP mechanism of action, in particular for what concerns the scarce capability to interact with the de novo formation of biofilm.

Extra hepatic expression of the acute phase protein alpha 1-acid glycoprotein in normal bovine tissues

Combined quantitative (real-time) polymerase chain reaction and immunohistochemistry were used to evaluate the expression of the minor acute phase protein alpha 1-acid glycoprotein (AGP, orosomucoid) in bovine extrahepatic tissues. AGP was produced mainly in the salivary glands and spleen, whereas minor expression was detected in all other tissues sampled, including lung, lymph nodes, uterus, ovary, kidney and tongue. The findings were consistent with immunohistochemical results. In view of the immunomodulatory and direct antibacterial activity of AGP, its expression in the salivary glands may signal an involvement in the regulation of the local immunity, even in non-pathological conditions.

Decreased sialylation of the acute phase protein alpha1-acid glycoprotein in feline infectious peritonitis (FIP).

Feline infectious peritonitis (FIP) is an immune-mediated disease of domestic and exotic felides infected with feline coronavirus. FIP is characterized by the overexpression of an acute phase protein, the α1-acid glycoprotein (AGP). In humans, AGP is a heavily glycosylated protein that undergoes several modifications of its glycan moiety during acute and chronic inflammatory pathologies. We studied the changes in AGP glycosylation in the course of FIP. Specifically, we focussed our attention on the degree of sialylation, fucosylation and branching. This study presents a purification method for feline AGP (fAGP) from serum, using an ion exchange chromatography strategy. The glycosylation pattern was analyzed in detail by means of interaction of purified fAGP with specific lectins. In particular, Sambucus nigra agglutinin I and Maackia amurensis agglutinin lectins were used to detect sialic acid residues, Aleuria aurantia lectin was used to detect l-fucose residues and Concanavalin A was used to evaluate the branching degree. By this method we showed that fAGP did not present any l-fucose residues on its surface, and that its branching degree was very low, both in normal and in pathological conditions. In contrast, during FIP disease, fAGP underwent several modifications in the sialic acid content, including decreased expression of both α(2–6)-linked and α(2–3)-linked sialic acid (76 and 44%, respectively when compared to non-pathological feline AGP).

Alpha 1-acid glycoprotein is an independent predictor of in-hospital death in the elderly.

to determine the contribution of the two acute phase proteins alpha 1-acid glycoprotein, and C-reactive protein to the prediction of overall mortality in hospitalised elderly patients. prospective cohort study. a department of geriatric medicine of Charles Richet Hospital, in the Paris-Ile de France area. 433 consecutive patients (mean age 84+/-7 years) admitted for rehabilitation in a department of geriatric medicine. clinical and laboratory examinations were performed at baseline. Follow-up ended at hospital discharge or death. Prognostic factors of survival were identified using Cox proportional hazards regression model. compared with the survivor group, the mean serum levels of both C-reactive protein and alpha 1-acid glycoprotein at baseline were higher in the deceased group (44+/-51 mg/l versus 22+/-34 mg/l and 1691+/-69 mg/l versus 1340+/-456 mg/l respectively; P<0.001 for each). Baseline levels of albumin and prealbumin were significantly lower in patients who died than in patients who survived. In multivariate analysis, alpha 1-acid glycoprotein (but not C-reactive protein), previous stroke, previous heart failure, and age emerged as the only parameters significantly and independently related to overall mortality. this study shows that the increase in plasma levels at admission of two acute-phase proteins, alpha 1-acid glycoprotein and C-reactive protein, were associated with in-hospital mortality in a population of hospitalised elderly patients. Furthermore, associations of overall mortality with inflammation differed among the markers and only alpha 1-acid glycoprotein entered the multivariate prediction model. Our findings support the hypothesis that alpha 1-acid glycoprotein may be superior to C-reactive protein in mortality risk assessment strategies for elderly patients.

Increased alpha3-fucosylation of alpha1-acid glycoprotein in Type I diabetic patients is related to vascular function.

Diabetic mellitus is attended by the development of endothelial dysfunction which is suggested to be accompanied with a chronic low-degree of inflammation. During a chronic hepatic inflammatory response, specific changes in glycosylation of the acute phase protein alpha1-acid glycoprotein (AGP) can be detected. In this report we studied the changes in glycosylation of AGP in more detail and evaluated the relation between a change in glycosylation of AGP and urinary albumin secretion in Type I diabetic patients. The glycosylation of AGP, studied by crossed affinity immunoelectrophoresis (CAIE) and high pH anion exchange chromatography with pulse amperometric detection (HPAEC-PAD), showed an increase in alpha3-fucosylation. Staining with an antibody against sialyl Lewis(x) (sLe(x)) implied that part of the alpha3-fucosylation was present in a sLe(x)-conformation. In the group of Type I diabetic patients with increased urinary albumin excretion, a significant increase in alpha3-fucosylation of AGP (p<0.0005) could be detected. Therefore, the increased alpha3-fucosylation of AGP can be used as an additional marker for the development of vascular complications in Type I diabetic patients.

Correlation between alpha 1-acid glycoprotein and total sialic acid in serum from dogs with tumours.

The influence of the acute phase protein alpha 1-acid glycoprotein (AGP) on the concentration of total sialic acid (TSA) in serum was investigated by assessing their degree of correlation in 115 clinically healthy dogs, 29 dogs with malignant mammary tumours, 12 dogs with various other malignant tumours, 12 dogs with benign mammary tumours and 10 dogs with various other benign tumours. Serum from dogs with malignant mammary tumours and other malignant tumours had a statistically significant correlation between AGP and TSA concentrations (Spearman correlation coefficient (rS) = 0.52, P = 0.0005, n = 41). The correlation was also statistically significant in dogs with benign mammary tumours and other benign tumours (rS = 0.48, P = 0.02, n = 22). The Spearman correlation coefficient was 0.51 (P = 0.0001, n = 63) in all dogs with tumours. This was also the case if only those dogs with levels of AGP comparable to healthy dogs (< 750 mg/l) were included in the analysis (rS = 0.42, P = 0.01, n = 56). In clinically healthy dogs, the correlation was not statistically significant (rS = 0.17, P = 0.07, n = 115). None of the four groups of dogs with tumours had changed serum AGP concentrations compared to clinically healthy dogs (all t-tests gave P values above 0.05). The serum concentrations of AGP did not correlate with the clinical stage of dogs with mammary tumours. In conclusion, AGP and TSA concentrations in serum are positively correlated in dogs with tumours, partially explaining the increase in serum TSA in these dogs. Increased sialylation of the AGP molecule in dogs with tumours might contribute to the increased serum TSA levels.

Alpha 1-acid glycoprotein and alpha 1-antitrypsin inhibit TNF-induced but not anti-Fas-induced apoptosis of hepatocytes in mice.

The acute phase proteins alpha 1-acid glycoprotein (alpha 1-AGP) and alpha 1-antitrypsin (alpha 1-AT) were shown to inhibit, by a mechanism unidentified to date, the lethality induced by TNF both in normal mice and in mice sensitized with galactosamine. We found that both bovine alpha 1-AGP and human alpha 1-AT also inhibited specifically the induction of apoptosis of hepatocytes by TNF/ galactosamine in vivo. This inhibition is specific for TNF, since apoptosis induced by TNF and actinomycin D was also inhibited, while similar apoptosis of hepatocytes induced by anti-Fas remained unaffected. The observation that these acute phase proteins did not affect the induction by TNF of IL-6, nitric oxide, or serum amyloid P excludes a nonselective inhibition of the TNF-activated pathways. The protection conferred by alpha 1-AGP and alpha 1-AT is presumably indirect, since these proteins did not inhibit TNF/actinomycin D-induced apoptosis in the hepatoma cell lines HepG2 and BWTG3.

Relation between pancreatic islet cellular infiltration and plasma fibrinogen or alpha 1-acid glycoprotein levels in spontaneously and streptozotocin-diabetic rats: an increase in these protein levels is not necessary for inducing microcirculatory erythrocyte velocity alteration.

Plasma levels of fibrinogen, alpha 1-acid glycoprotein (AG) and albumin, pancreatic insulitis quantitative scores, and erythrocyte velocity in the mesoappendix microvessels were measured in BB diabetic (BBD) and streptozotocin-diabetic rats (WSTZ) in order to answer the following questions: (a) Does hyperfibrinogenemia or increase in AG plasma level occur in BBD and WSTZ rats, and if so, are these alterations secondary to the hyperglycemia or to an inflammatory process such as insulitis? (b) Is there a decrease in microcirculatory flow in the BBD and WSTZ rats, and if so, is it secondary to the hyperfibrinogenemia and/or the hyperglycemia? Insulitis was present in the BBD rats after 5 weeks of disease (with a score of 2.9 +/- 0.1 vs. 1.4 +/- 0.6 in the normoglycemic controls), but absent in WSTZ rats after 5 months of disease (1.2 +/- 0.06 vs. 1.1 +/- 0.06). Increase in fibrinogen and AG plasma levels was observed in the BBD rats only and appears linked to the insulitis. The major acute phase protein AG level is increased in BBD rats already on the first day of appearance of glycosuria. In the WSTZ rats, without insulitis, chronic hyperglycemia alone did not induce an increase in fibrinogen and AG plasma levels. A decreased microcirculatory erythrocyte velocity has been found in both BBD and WSTZ rats. Thus an increase in fibrinogen or AG plasma levels is not necessary for inducing a decrease in erythrocyte velocity. Hyperglycemia is probably the main factor responsible for the decrease in microcirculatory flow in the BBD and WSTZ rats.

Acute phase mediators and glucocorticoids elevate alpha 1-acid glycoprotein gene transcription.

Acute phase mediators and glucocorticoids increase the synthesis of the acute phase protein alpha 1-acid glycoprotein, also known as orosomucoid, by inducing the hepatic level of its mRNA. Concurrently the acute phase response depresses the hepatic synthesis of albumin and alpha 2u-globulin and their mRNA levels. Present transcriptional studies in isolated liver nuclei demonstrate that turpentine-induced acute phase mediators simultaneously enhance transcription of the alpha 1-acid glycoprotein gene and diminish transcription of albumin and alpha 2u-globulin genes; parallel alterations in the hepatic level of the corresponding mRNAs ensue. The present transcriptional studies also demonstrate that administration of dexamethasone to adrenalectomized rats dramatically elevates the rate of transcription of the alpha 1-acid glycoprotein gene as well as the alpha 2u-globulin and the albumin genes, leading to elevations in alpha 1-acid glycoprotein and alpha 2u-globulin hepatic mRNA levels. Thus, hepatic alpha 1-acid glycoprotein mRNA levels are predominantly regulated in vivo at the transcriptional level by glucocorticoids as well as by acute phase mediators.

Early plasma protein and mineral changes after surgery: a two stage process.

Sequential changes in albumin, transferrin, alpha 1-acid glycoprotein, C reactive protein, fibrinogen, copper, iron, and zinc in plasma up to 24 h after hysterectomy were measured. No increases in the concentrations of the acute phase proteins alpha 1-acid glycoprotein, C reactive protein, and fibrinogen were observed until 6 h after the skin incision. These increases were preceded by significant falls at 2-4 h, and this was shown also by albumin, transferrin, iron, zinc, and copper. The ratios of iron and zinc to their binding proteins, transferrin and albumin, did not decrease until 4-6 h and their concentrations remained low for at least 24 h. These patterns suggest that at least two mechanisms operate after trauma. The early fall in the concentrations of the proteins in plasma is consistent with a prompt increase in microvascular permeability. The later decrease in binding of the metals iron and zinc to their transport proteins and the increase in concentrations of the acute phase proteins could be initiated by a common mediator.