Acute phase response in zebrafish embryo/larva with special emphasis on LPS-induced changes in expression pattern of acute phase protein genes

Acute phase response (APR) in developing embryos/larvae remains poorly studied in fish, and information regarding the expression and role of acute phase proteins (APPs) in developing embryos/larvae is rather limited in teleosts. In this study we investigated the APR in zebrafish (Danio rerio) embryos/larvae challenged with LPS by examining the expression of APP genes encoding CRP, SAA, LECT2, HAMP and HP and APP inducer genes encoding IL-1β and TNF-α. Expression of all the seven genes was up-regulated in embryos/larvae after challenge with LPS as revealed by q-RT-PCR. Whole-mount in situ hybridization (WISH) showed that all the genes displayed strong maternal expression in the cleavage and blastula stages, and ubiquitous expression in the gastrula and segmentation stage embryos, and then they were expressed differently in specific tissues in later developmental stages. Interestingly, challenge with LPS resulted in de novo expression of the SAA gene in the yolk sac and intestine, the LECT2 gene in the yolk sac, and the IL-1β gene in the yolk sac and the dispersed neutrophils of caudal vein, and visible enhanced expression of the LECT2 gene in the yolk sac. These are the first such data reported in teleosts, showing that LPS challenge is able to modify the expression patterns of APP and APP inducer genes. Altogether, these data suggest that zebrafish embryos/larvae are able to respond to acute infection though their immune system remains in a developing and immature state.

Download Full-text

The acute phase response and C-reactive protein

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0239 ◽

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.

Download Full-text

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

Canadian Journal of Applied Physiology ◽

10.1139/h05-115 ◽

2005 ◽

Vol 30 (2) ◽

pp. 196-211 ◽

Cited By ~ 6

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

Download Full-text

Monokines regulate glycosylation of acute-phase proteins.

Journal of Experimental Medicine ◽

10.1084/jem.166.1.253 ◽

1987 ◽

Vol 166 (1) ◽

pp. 253-258 ◽

Cited By ~ 67

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.

Download Full-text

Acute Phase Proteins in the Acute Phase Response

10.1007/978-1-4471-1739-1 ◽

1989 ◽

Cited By ~ 4

Keyword(s):

Acute Phase ◽

Acute Phase Response ◽

Acute Phase Proteins ◽

Phase Response

Download Full-text

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

Veterinární Medicína ◽

10.17221/7478-vetmed ◽

2014 ◽

Vol 59 (No. 4) ◽

pp. 163-180 ◽

Cited By ~ 73

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.  

Download Full-text

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

Journal of Experimental Medicine ◽

10.1084/jem.156.4.1268 ◽

1982 ◽

Vol 156 (4) ◽

pp. 1268-1273 ◽

Cited By ~ 29

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.

Download Full-text

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

Journal of Virology ◽

10.1128/jvi.79.8.5174-5184.2005 ◽

2005 ◽

Vol 79 (8) ◽

pp. 5174-5184 ◽

Cited By ~ 36

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.

Download Full-text

The influence of glucocorticoid on the fibrinogen messenger RNA content of rat liver in vivo and in hepatocyte suspension culture

Biochemical Journal ◽

10.1042/bj2200631 ◽

1984 ◽

Vol 220 (3) ◽

pp. 631-637 ◽

Cited By ~ 17

Author(s):

H M G Princen ◽

H J Moshage ◽

H J W de Haard ◽

P J van Gemert ◽

S H Yap

Keyword(s):

Acute Phase ◽

Acute Phase Response ◽

Messenger Rna ◽

Acute Phase Proteins ◽

Rat Hepatocytes ◽

Phase Response ◽

Control Value ◽

Hepatocyte Suspension

The plasma concentration of fibrinogen, one of the major acute-phase proteins produced by the liver, increases during the acute-phase response as a result of enhanced synthesis in liver. Since adrenal-cortical hormones have been thought to have a key role in the regulation of the fibrinogen synthesis, fibrinogen-polypeptide mRNA sequences were determined in the present study, by using a specific complementary-DNA probe, in RNA fractions obtained from rat hepatocytes exposed to glucocorticoids in vitro (hepatocyte suspension cultures) and in vivo. Maximal induction of the fibrinogen-polypeptide mRNA (to 400% of the control value) was found in vitro at 0.1 microM-dexamethasone after 9 h of incubation. The same magnitude of induction was obtained with 20 microM-cortisol or 60 microM-corticosterone. In contrast with the findings in vitro, no induction of the fibrinogen-polypeptide mRNA was observed in the liver at various times after injection of different doses of glucocorticoids into rats. These results suggest that more complex regulatory mechanisms are involved and that glucocorticoids are not the sole regulatory factors in vivo in the enhanced synthesis of fibrinogen during the acute-phase response.

Download Full-text