Acute phase reaction and acute phase proteins

A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations.

A survey of biochemical and acute phase proteins changes in sheep experimentally infected with Anaplasma ovis

Objective: To determine the biochemical and acute phase proteins changes in sheep experimentally infected with Anaplasma ovis(A. ovis). Methods: One Iranian sheep naturally infected with A. ovis(parasitemia 0.02%) but with no other blood parasites based on blood smear and polymerase chain reaction methods was selected as donor, and it was splenectomized to induce high level of parasitemia. Then, three weeks after splenectomy when parasitemia was 6%, donor's blood was intravenously administered to each recipient animal. Five 5-6 months old Iranian male sheep without any blood parasites were selected as recipient animals. The percent of parasites, packed cell volume, serum biochemical parameters(urea, creatinine, bilirubin, aspartate aminotransferase activity, cholesterol, total protein, albumin, globulin, Fe), acute phase proteins(haptoglobin, total iron binding capacity, fibrinogen), were evaluated in sheep before and after being experimentally infected with A. ovis(until day 38). In addition, body weights of sheep were measured on days 0, 20 and 38. Results: In recipient sheep, microscopic examination of erythrocytes revealed a significant rise of parasitemia on days 12 and 15. The lowest level of packed cell volume in sheep was seen on day 15 post infection. A significant rise existed in mean urea and bilirubin(total, direct and indirect) on days 15 and 20. The increase of indirect bilirubin level was higher than direct bilirubin. Furthermore, serum Fe significantly increased on days 20 and 23. The mean total protein concentration significantly increased on day 38. A significant increase was found in the serum globulin concentration from days 20 and 27 to 38. Maximum values of haptoglobin were observed on days 27 and 30. Moreover, aspartate aminotransferase activity(from days 20-30) and cholesterol concentration(on day 20) significantly decreased. However, no significant changes were found in other parameters. Conclusions: Experimental ovine anaplasmosis caused by A. ovis could be associated with some changes in measured parameters, which presumably could be helpful for evaluation on staging of disease.

Comparative evaluation of acute phase proteins by C-reactive protein(CRP)and serum amyloid A(SAA)in nonhuman primates and feline carnivores

The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals.

Clinical and Experimental Study of Effect on Acute Phase Protein of Multiple Organ Dysfunction Syndrome Treated with Dachengqi Decoction

Objective: To investigate the level of acute phase proteins (APP)-synthesized in hepatocytes in pathogenic process of multiple organ dysfunction syndrome (MODS) and the effect of Dachengqi Decoction (DCQD) on it. Methods: The levels of C-reactive protein (CRP),α1-acid glycoprotein (AAG), α1-antitrypsin total (α1AT), α2-macroglobulin (α2-MG), ceruloplasmine (CP), hepatoglobin (HP) and transferrin (TF) synthesis were determined in 32 cases of MODS patients and rat models of MODS induced by acute infective peritonitis and mesenterial artery ischemia-reperfusion.Results: The serum APP level in MODS patients was increased and higher than that in the control group (P < 0. 01 ). After 3 days of DCQD treatment it reduced significantly (P <0. 05). Serum APP level in MODS model was also increased significantly, and after 3 days of DCQD treatment, it reduced significantly (P < 0. 05). The APP secreting level of rat hepatocytes cultured in vitro raised after stimulated and activated by lipopolysacchride, which was reduced after cultured with rabbits serum containing different concentration of effective ingredients of DCQD. The APP inhibiting effect of DCQD was dose dependent. Conclusion: Purgation therapy with DCQD could reduce the stimulation of pathogenic factors on hepatocytes, protect tissues and organs from damage caused by excessive inflammatory reaction.Original article on CJIM(Chin) 1998; 18(8): 453

Proteomic approach for acute-phase proteins of hemolymph and muscles in Scylla serrata challenged by a pathogenic bacterium

Acute-phase response is documented to be a significant mechanism of innate immunity in vertebrates and invertebrates.In this study,proteomic methodologies were applied for different protein expressions in hemolymph of Scylla serrata challenged by Vibrio parahaemolyticus after immunization,and in muscles of the crabs separately chal-lenged by V.parahaemolyticus,V.anguillarum and Aeromonas hydrophila.Up-regulated cryptocyanin is documented in the hemolymph and up-regulated calexcitin,wingless(fragment)and tachykinin-related peptide in the muscle as acute-phase proteins.All the four altered proteins were responsible for bacterial stress,but cryptocyanin seemed to be a memory response protein against the chal-lenge by a live bacterium after immunization of the live cells.These up-regulated proteins can be indicative of an understanding of immunity of a crab.

Lipopolysaccharide immune stimulation but not β-mannanase supplementation affects maintenance energy requirements in young weaned pigs

Background: Pathogen or diet-induced immune activation can partition energy and nutrients away from growth,but clear relationships between immune responses and the direction and magnitude of energy partitioning responses have yet to be elucidated. The objectives were to determine how β-mannanase supplementation and lipopolysaccharide(LPS) immune stimulation affect maintenance energy requirements(MEm) and to characterize immune parameters, digestibility, growth performance, and energy balance.Methods: In a randomized complete block design, 30 young weaned pigs were assigned to either the control treatment(CON; basal corn, soybean meal and soybean hul s diet), the enzyme treatment(ENZ; basal diet + 0.056% β-mannanase),or the immune system stimulation treatment(ISS; basal diet + 0.056% β-mannanase, chal enged with repeated increasing doses of Escherichia coli LPS). The experiment consisted of a 10-d adaptation period, 5-d digestibility and nitrogen balance measurement, 22 h of heat production(HP) measurements, and 12 h of fasting HP measurements in indirect calorimetry chambers. The immune chal enge consisted of 4 injections of either LPS(ISS) or sterile saline(CON and ENZ), one every48 h beginning on d 10. Blood was collected pre-and post-challenge for complete blood counts with differential,haptoglobin and mannan binding lectin, 12 cytokines, and glucose and insulin concentrations.Results: Beta-mannanase supplementation did not affect immune status, nutrient digestibility, growth performance,energy balance, or MEm. The ISS treatment induced fever, elevated proinflammatory cytokines and decreased leukocyte concentrations(P < 0.05). The ISS treatment did not impact nitrogen balance or nutrient digestibility(P > 0.10),but increased total HP(21%) and MEm(23%), resulting in decreased lipid deposition(-30%) and average daily gain(-18%)(P < 0.05).Conclusions: This experiment provides novel data on β-mannanase supplementation effects on immune parameters and energy balance in pigs and is the first to directly relate decreased ADG to increased MEm independent of changes in feed intake in immune challenged pigs. Immune stimulation increased energy partitioning to the immune system by 23% which limited lipid deposition and weight gain. Understanding energy and nutrient partitioning in immune-stressed pigs may provide insight into more effective feeding and management strategies.

Breed and adaptive response modulate bovine peripheral blood cells＇ transcriptome

Background： Adaptive response includes a variety of physiological modifications to face changes in external or internal conditions and adapt to a new situation. The acute phase proteins（APPs） are reactants synthesized against environmental stimuli like stress, infection, inflammation.Methods： To delineate the differences in molecular constituents of adaptive response to the environment we performed the whole-blood transcriptome analysis in Italian Holstein（IH） and Italian Simmental（IS） breeds. For this, 663 IH and IS cows from six commercial farms were clustered according to the blood level of APPs. Ten extreme individuals（five APP＋ and APP-variants） from each farm were selected for the RNA-seq using the Illumina sequencing technology. Differentially expressed（DE） genes were analyzed using dynamic impact approach（DIA）and DAVID annotation clustering. Milk production data were statistically elaborated to assess the association of APP＋ and APP-gene expression patterns with variations in milk parameters.Results： The overall de novo assembly of cDNA sequence data generated 13,665 genes expressed in bovine blood cells. Comparative genomic analysis revealed 1,152 DE genes in the comparison of all APP＋ vs. all APP-variants; 531 and 217 DE genes specific for IH and IS comparison respectively. In all comparisons overexpressed genes were more represented than underexpressed ones. DAVID analysis revealed 369 DE genes across breeds, 173 and 73 DE genes in IH and IS comparison respectively. Among the most impacted pathways for both breeds were vitamin B6 metabolism, folate biosynthesis, nitrogen metabolism and linoleic acid metabolism.Conclusions： Both DIA and DAVID approaches produced a high number of significantly impacted genes and pathways with a narrow connection to adaptive response in cows with high level of blood APPs. A similar variation in gene expression and impacted pathways between APP＋ and APP-variants was found between two studied breeds. Such similarity was also confirmed by annotation clustering of the DE genes. However, IH breed showed higher and more differentiated impacts compared to IS breed and such particular features in the IH adaptive response could be explained by its higher metabolic activity. Variations of milk production data were significantly associated with APP＋ and APP-gene expression patterns.

Hepatocytes： a key cell type for innate immunity

Hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. Hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. These proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron-sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide signaling, and the coagulation factor fibrinogen that activates innate immunity. In this review, we summarize the wide variety of innate immunity proteins produced by hepatocytes and discuss liver-enriched transcription factors （e.g. hepatocyte nuclear factors and CCAAT/enhancer-binding proteins）, pro-inflammatory mediators （e.g. interleukin （IL）-6, IL-22, IL-lp and tumor necrosis factor-a）, and downstream signaling pathways （e.g. signal transducer and activator of transcription factor 3 and nuclear factor-KB） that regulate the expression of these innate immunity proteins. We also briefly discuss the dysregulation of these innate immunity proteins in chronic liver disease, which may contribute to an increased susceDtibilitv to bacterial infection in oatients with cirrhosis.

Dynamic changes of serum cholinesterase activity after severe trauma

Objective： The aim of the present study was to examine dynamic changes in serum cholinesterase （ChE） activity during early-stage severe trauma and the clinical significance of these changes. Methods： This prospective, observational study included 81 patients with severe trauma who were treated between October 2011 and April 2013 in the emergency intensive care unit （EICU） of a university-affiliated, tertiary-care, grade A general hospital in China. Serum ChE activity was measured on Days 1, 3, and 7 post-injury. The correlation of dynamic changes in serum ChE activity with trauma severity and prognosis was assessed. Correlations between changes in serum ChE activity after injury and albumin （ALB）, prealbumin （PAB）, transferrin （TRF）, and C-reactive protein （CRP） levels were also analyzed Results： Serum ChE activity in trauma patients was 42.3%-50.2% lower on Days 1, 3, and 7 compared with the control （P〈0.001 for all time points）, and it continued to decrease after Day 7 in both the survival and death subgroups. In the subgroup with an injury severity score （ISS） of 〈25, serum ChE activity initially decreased, but eventually increased. However, activity decreased continuously in the ISS〉25 subgroup. ChE activity was significantly lower in both the death and the ISS〉25 subgroups than in the survival and ISS〈25 subgroups on Days 1, 3, and 7 after injury. Activity was negatively correlated with ISS and acute physiology and chronic health evaluation Ill （APACHE III） at all time points. When comparing the receiver operating characteristic （ROC） curves for predicting prognosis, the area under the curve （AUC） in the dot of serum ChE was similar to the AUCs in plots of ISS and APACHE Ⅲ, but significantly smaller than the AUC in the plot of the trauma and injury severity score （TRISS）. Serum ChE activity was positively correlated with ALB, PAB, and TRF at all time points post-injury. Activity was not significantly correlated with CRP on Day 1, but was significantly and negatively correlated with CRP on Days 3 and 7. Conclusions： There is a significant decrease in serum ChE activity after severe trauma. Serum ChE may be regarded as a negative acute phase protein （APP） and the dynamic changes in serum ChE may be useful as an auxiliary indicator for evaluating trauma severity and predicting prognosis.