scholarly journals The Acute Phase Response Is a Prominent Renal Proteome Change in Sepsis in Mice

2019 ◽  
Vol 21 (1) ◽  
pp. 200 ◽  
Author(s):  
Beáta Róka ◽  
Pál Tod ◽  
Tamás Kaucsár ◽  
Matej Vizovišek ◽  
Robert Vidmar ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Mrna Expression ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Late Phase ◽  
Kidney Injury ◽  
Phase Response ◽  
Complement C3 ◽  
Saline Control

(1) Background: Sepsis-induced acute kidney injury (AKI) is the most common form of acute kidney injury (AKI). We studied the temporal profile of the sepsis-induced renal proteome changes. (2) Methods: Male mice were injected intraperitoneally with bacterial lipopolysaccharide (LPS) or saline (control). Renal proteome was studied by LC-MS/MS (ProteomeXchange: PXD014664) at the early phase (EP, 1.5 and 6 h after 40 mg/kg LPS) and the late phase (LP, 24 and 48 h after 10 mg/kg LPS) of LPS-induced AKI. Renal mRNA expression of acute phase proteins (APP) was assessed by qPCR. (3) Results: Renal proteome change was milder in EP vs. LP. APPs dominated the proteome in LP (proteins upregulated at least 4-fold (APPs/all): EP, 1.5 h: 0/10, 6 h: 1/10; LP, 24 h: 22/47, 48 h: 17/44). Lipocalin-2, complement C3, fibrinogen, haptoglobin and hemopexin were the most upregulated APPs. Renal mRNA expression preceded the APP changes with peak effects at 24 h, and indicated renal production of the majority of APPs. (4) Conclusions: Gene expression analysis revealed local production of APPs that commenced a few hours post injection and peaked at 24 h. This is the first demonstration of a massive, complex and coordinated acute phase response of the kidney involving several proteins not identified previously.

scholarly journals Comparison of Inflammatory and Acute-Phase Responses in the Brain and Peripheral Organs of the ME7 Model of Prion Disease

2005 ◽  
Vol 79 (8) ◽  
pp. 5174-5184 ◽  
Author(s):  
Colm Cunningham ◽  
David C. Wilcockson ◽  
Delphine Boche ◽  
V. Hugh Perry
Keyword(s):  
Prion Disease ◽  
Acute Phase ◽  
Proinflammatory Cytokines ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Phase Response ◽  
Complement C3 ◽  
Significant Elevation ◽  
Cns Inflammation ◽  
Amyloid A

ABSTRACT Chronic neurodegenerative diseases such as prion disease and Alzheimer's disease (AD) are reported to be associated with microglial activation and increased brain and serum cytokines and acute-phase proteins (APPs). Unlike AD, prion disease is also associated with a peripheral component in that the presumed causative agent, PrPSc, also accumulates in the spleen and other lymphoreticular organs. It is unclear whether the reported systemic acute-phase response represents a systemic inflammatory response to prion disease or merely reflects central nervous system (CNS) inflammation. For this study, we investigated whether intracerebrally initiated prion disease (ME7 model) provokes splenic, hepatic, or brain inflammatory and acute-phase responses. We detected no significant elevation of proinflammatory cytokines or activation of macrophages in the spleens of these animals, despite clear PrPSc deposition. Similarly, at 19 weeks we detected no significant elevation of transcripts for the APPs serum amyloid A, complement C3, pentraxin 3, and α2-antiplasmin in the liver, despite CNS neurodegeneration and splenic PrPSc deposition at this time. However, despite the low CNS expression levels of proinflammatory cytokines, there was robust expression of these APPs in degenerating brains. These findings suggest that PrPSc is not a stimulus for splenic macrophages and that neither peripheral PrPSc deposition nor CNS neurodegeneration is sufficient to produce a systemic acute-phase response. We also propose that serum cytokine and APP measurements are not useful during preclinical disease. Possible consequences of the clear chronic elevation of APPs in the CNS are discussed.

scholarly journals FP294TEMPORAL PROFILE OF THE RENAL ACUTE PHASE RESPONSE IN SEPSIS-INDUCED ACUTE KIDNEY INJURY IN MICE

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Beáta Róka ◽  
Pál Tod ◽  
Tamás Kaucsár ◽  
Marco Fonović ◽  
Boris Turk ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Kidney Injury ◽  
Phase Response

The acute phase response and C-reactive protein

2020 ◽  
pp. 2199-2207
Author(s):  
Mark B. Pepys
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Serum Amyloid A ◽  
Acute Phase Proteins ◽  
Phase Response ◽  
Serum Amyloid ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Amyloid A ◽  
Serum Amyloid A Protein

The acute phase response—trauma, tissue necrosis, infection, inflammation, and malignant neoplasia induce a complex series of nonspecific systemic, physiological, and metabolic responses including fever, leucocytosis, catabolism of muscle proteins, greatly increased de novo synthesis and secretion of a number of ‘acute phase’ plasma proteins, and decreased synthesis of albumin, transthyretin, and high- and low-density lipoproteins. The altered plasma protein concentration profile is called the acute phase response. Acute phase proteins—these are mostly synthesized by hepatocytes, in which transcription is controlled by cytokines including interleukin 1, interleukin 6, and tumour necrosis factor. The circulating concentrations of complement proteins and clotting factors increase by up to 50 to 100%; some of the proteinase inhibitors and α‎1-acid glycoprotein can increase three- to fivefold; but C-reactive protein (CRP) and serum amyloid A protein (an apolipoprotein of high-density lipoprotein particles) are unique in that their concentrations can change by more than 1000-fold. C-reactive protein—this consists of five identical, nonglycosylated, noncovalently associated polypeptide subunits. It binds to autologous and extrinsic materials which contain phosphocholine, including bacteria and their products. Ligand-bound CRP activates the classical complement pathway and triggers the inflammatory and opsonizing activities of the complement system, thereby contributing to innate host resistance to pneumococci and probably to recognition and safe ‘scavenging’ of cellular debris. Clinical features—(1) determination of CRP in serum or plasma is the most useful marker of the acute phase response in most inflammatory and tissue damaging conditions. (2) Acute phase proteins may be harmful in some circumstances. Sustained increased production of serum amyloid A protein can lead to the deposition of AA-type, reactive systemic amyloid.

Immune Alterations, Lipid Peroxidation, and Muscle Damage Following a Hill Race

2005 ◽  
Vol 30 (2) ◽  
pp. 196-211 ◽  
Author(s):  
Richard J. Simpson ◽  
Martin R. Wilson ◽  
James R. Black ◽  
James A. Ross ◽  
Greg P. Whyte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Muscle Damage ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Venous Blood ◽  
Total Antioxidant Status ◽  
Phase Response ◽  
Tnf Α

Hill races usually include large downhill running sections, which can induce significant degrees of muscle damage in a field setting. This study examined the link between muscle damage, oxidative stress, and immune perturbations following a 7-km mountainous hill race with 457 m of ascent and 457 m of descent. Venous blood samples were taken from 7 club level runners before, immediately after, and 48 hrs postrace. Samples were analysed for total and differential leukocyte counts, markers of muscle damage (CK), lipid peroxidation (MDA), and acute phase proteins (CRP; fibrinogen; α-1-ACT). The total antioxidant status (TEAC) and plasma levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α were also determined. Subjective pain reports, and plasma activities of CK, MDA, and circulatory monocytes reached peak values at 48 hrs postrace (p <  0.05). TEAC and the cytokine IL-8 increased immediately after the race (p <  0.05). Plasma TNF-α remained unchanged (p > 0.05). Despite the reports of muscle damage and soreness, no evidence of an acute phase response was observed (p > 0.05), which may be explained by the failure of the race to induce a plasma TNF-α response. Future studies should examine the link between muscle damage, oxidative stress, and the acute phase response following hill races of longer duration with larger eccentric components. Key words: acute phase response, cytokines, antioxidant capacity, creatine kinase, field study

scholarly journals Monokines regulate glycosylation of acute-phase proteins.

1987 ◽  
Vol 166 (1) ◽  
pp. 253-258 ◽  
Author(s):  
A Mackiewicz ◽  
M K Ganapathi ◽  
D Schultz ◽  
I Kushner
Keyword(s):  
Cell Line ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Hepatoma Cell ◽  
Phase Response ◽  
Hepatoma Cell Line ◽  
Human Hepatoma Cell ◽  
Inflammatory Stimuli ◽  
Necrosis Factor

The acute-phase response to inflammatory stimuli, characterized by increased synthesis of acute-phase proteins (APP), is often accompanied by changes in the glycosylation patterns of some of these proteins. While expression of APP genes in hepatocytes is regulated by monokines, mechanisms governing changes in glycosylation are not known. Exposure of human hepatoma cell line Hep 3B to conditioned medium from LPS-activated human monocytes and to medium from the keratocarcinoma cell line COLO-16 led to increased synthesis of alpha 1 proteinase-inhibitor and ceruloplasmin and to alterations of their glycosylation patterns similar to those seen in human serum in various inflammatory states. IL-1, tumor necrosis factor, and hepatocyte stimulating factor I increased synthesis of ceruloplasmin without alterations in the pattern of its glycosylation. These findings demonstrate that altered glycosylation seen in plasma in some inflammatory states can be explained by the effects of monokines on glycosylation in hepatocytes and that gene expression and glycosylation of some APP during the acute-phase response may be regulated by different mechanisms.

scholarly journals Acute phase proteins and their use in the diagnosis of diseases in ruminants: a review

2014 ◽  
Vol 59 (No. 4) ◽  
pp. 163-180 ◽  
Author(s):  
C. Tothova ◽  
O. Nagy ◽  
G. Kovac
Keyword(s):  
Clinical Application ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Phase Response ◽  
Farm Animals ◽  
Wide Range ◽  
New Biomarkers ◽  
Treatment Prognosis ◽  
Hepatic Synthesis

The acute phase response is a complex systemic early-defence system of reactions activated by trauma, infection, tissue damage, inflammation, stress or neoplasia. One of the most important elements of this response is the increased hepatic synthesis of some plasma proteins, collectively known as acute phase proteins. The discovery of these new biomarkers has allowed the clinical monitoring of different diseases; therefore, their clinical application has been studied widely in human medicine in order to improve the diagnosis, evaluation, treatment, prognosis and therapeutics of many diseases. Although a wide range of studies have been carried out to determine the usefulness of acute phase proteins in several diseases also in animals, they are still relatively under-utilised in veterinary medicine, predominantly in farm animals. The acute phase response and clinical application of acute phase proteins in ruminants are reviewed in this article, including their diagnostic use in clinical practice and application in the monitoring of treatment, which is one of the most promising practical uses of these proteins. &nbsp;

In vivo regulation of plasma platelet-activating factor acetylhydrolase during the acute phase response

1999 ◽  
Vol 277 (1) ◽  
pp. R94-R103 ◽  
Author(s):  
Riaz A. Memon ◽  
John Fuller ◽  
Arthur H. Moser ◽  
Kenneth R. Feingold ◽  
Carl Grunfeld
Keyword(s):  
Mrna Expression ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Platelet Activating Factor ◽  
Phase Response ◽  
Mrna Levels ◽  
Potent Inducer ◽  
Platelet Activating Factor Acetylhydrolase ◽  
Infection And Inflammation ◽  
Lps Treatment

Plasma platelet-activating factor acetylhydrolase (PAF-AH) hydrolyzes PAF and oxidized phospholipids and is associated with lipoproteins in the circulation. Endotoxin [lipopolysaccharide (LPS)], a potent inducer of the acute phase response (APR), produces marked changes in several proteins that play important roles in lipoprotein metabolism. We now demonstrate that LPS produces a 2.5- to 3-fold increase in plasma PAF-AH activity in Syrian hamsters. The plasma PAF-AH activity is found in the high-density lipoprotein (HDL) fraction and is increased threefold with LPS treatment despite a decrease in plasma HDL levels, indicating that plasma PAF-AH activity is increased per HDL particle. LPS markedly increased PAF-AH mRNA levels in liver, spleen, lung, and small intestine. The maximal increase in plasma PAF-AH activity and mRNA expression in liver and spleen is seen 24 h after LPS treatment. Both tumor necrosis factor and interleukin-1 modestly increased plasma PAF-AH activity and mRNA levels in liver and spleen, suggesting that they may partly mediate the effect of LPS on PAF-AH. Surgical removal of spleen had no effect on basal or LPS-induced plasma PAF-AH activity, suggesting that spleen per se may not contribute to plasma PAF-AH activity. Finally, LPS, turpentine and zymosan increased plasma PAF-AH activity in mice and/or rats, indicating that multiple APR inducers upregulate plasma PAF-AH and this effect is consistent across different rodent species. Taken together, our results indicate that plasma PAF-AH activity and mRNA expression is markedly upregulated during the host response to infection and inflammation. An increase in plasma PAF-AH may enhance the degradation of PAF as well as alter the structure and function of HDL during infection and inflammation.

scholarly journals The acute-phase response in (NZB X NZW)F1 and MRL/l MICE.

1982 ◽  
Vol 156 (4) ◽  
pp. 1268-1273 ◽  
Author(s):  
C Rordorf ◽  
H P Schnebli ◽  
M L Baltz ◽  
G A Tennent ◽  
M B Pepys
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Acute Phase Protein ◽  
Phase Response ◽  
Serum Amyloid ◽  
Human Rheumatoid Arthritis ◽  
Amyloid A ◽  
Serum Amyloid A Protein ◽  
Phase Protein

The acute-phase plasma protein response to disease activity in murine models of autoimmune lupus-like disease was investigated by measurement of the concentration of serum amyloid P component (SAP) in NZB X W and MRL/l mice. The levels of SAP, which is a major acute-phase protein in mice, did not rise at all in response to progression of disease in NZB X W mice between the ages of 1 and 9 mo. This resembles the behavior of acute-phase proteins such as C-reactive protein and serum amyloid A protein in human systemic lupus erythematosus, and just as in human lupus, where the occurrence of intercurrent microbial infection can stimulate an acute-phase response, so injection of bacterial lipopolysaccharide or casein into the NZB X W mice stimulated "normal" acute-phase SAP production. In marked contrast, MRL/l mice developed greatly increased levels of SAP, which correlated closely with progression of their pathology as they aged. The disease profile of the MRL/l strain includes rheumatoid factors and spontaneous polyarthritis and their SAP response resembles the behavior of acute phase proteins in human rheumatoid arthritis. Different patterns of acute-phase response in different autoimmune disorders may thus be a reflection of the genetic predisposition to particular diseases and/or contribute to their pathogenesis. The existence of animal counterparts for the various clinical patterns of human acute-phase protein production will assist in experimental investigation of the underlying mechanisms and of the biological role of the acute-phase response.

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