The Effect of Factor Xa/Phospholipid Infusion on the Acute Phase Response in Baboons

1997 ◽  
Vol 77 (02) ◽  
pp. 308-311 ◽  
Author(s):  
Egbert K O Kruithof ◽  
Diane Agay ◽  
Jean Claude Mestries ◽  
Marie-Paule Gascon ◽  
Arnaud Ythier
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Response ◽  
Tissue Injury ◽  
Peak Plasma ◽  
Factor Xa ◽  
Phase Response ◽  
C Reactive Protein ◽  
Reactive Protein

SummaryDisseminated intravascular coagulation (DIC) is a frequent complication of septicemia or tissue injury and may be accompanied by elevations of interleukin-6, a mediator of the acute phase response. It is not known whether thrombin or fibrin deposition may directly induce an acute phase response. To study this, we employed a baboon model of in vivo thrombin generation, induced by the administration of purified bovine Factor Xa and phospholipid vesicles. Two Xa/phospholipid dosages were used, a low dosage (2 animals) leading to a rapid 49% decrease in fibrinogen and a high dosage (two injections at 5h interval; 3 animals) leading to complete fibrinogen depletion. Thereafter, fibrinogen levels increased in both treatment groups, reached a maximum of 2.52 ± 0.23 g/1 (mean ± SE, n = 5; p <0.01 with respect to basal levels) at day 2, and returned to normal by day seven. In five control (injection of 0.15% NaCl) baboons no significant changes of fibrinogen were observed (maximal values: 1.88 ± 0.12 g/1). Serum concentrations of C-reactive protein, an acute phase protein, increased from 3.7 ± 0.4 mg/1 to a maximum of 33.0 ± 7.3 at day one, which was five-fold higher (p <0.01) than in control animals at day one (6.2 ± 0.5 mg/1). Transient increases were observed within 6 h for interleukin-6 from basal values of 6.2 ± 1.7 ng/1 to peak plasma levels of 42.9 ±21.4 ng/1, a value threefold higher (p = 0.07) than in control animals (14.8 ± 4.0 ng/1).The preliminary results of this observational study suggest that factor Xa/phospholipid infusion is followed by an acute phase response, leading after one day to significant increases of fibrinogen and of C-reactive protein.

scholarly journals C-Reactive Protein and Complement Are Important Mediators of Tissue Damage in Acute Myocardial Infarction

1999 ◽  
Vol 190 (12) ◽  
pp. 1733-1740 ◽  
Author(s):  
M. Griselli ◽  
J. Herbert ◽  
W.L. Hutchinson ◽  
K.M. Taylor ◽  
M. Sohail ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Myocardial Injury ◽  
Peak Plasma ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Coronary Ligation

Myocardial infarction in humans provokes an acute phase response, and C-reactive protein (CRP), the classical acute phase plasma protein, is deposited together with complement within the infarct. The peak plasma CRP value is strongly associated with postinfarct morbidity and mortality. Human CRP binds to damaged cells and activates complement, but rat CRP does not activate complement. Here we show that injection of human CRP into rats after ligation of the coronary artery reproducibly enhanced infarct size by ∼40%. In vivo complement depletion, produced by cobra venom factor, completely abrogated this effect. Complement depletion also markedly reduced infarct size, even when initiated up to 2 h after coronary ligation. These observations demonstrate that human CRP and complement activation are major mediators of ischemic myocardial injury and identify them as therapeutic targets in coronary heart disease.

scholarly journals Regulated export of a secretory protein from the ER of the hepatocyte: a specific binding site retaining C-reactive protein within the ER is downregulated during the acute phase response.

1992 ◽  
Vol 118 (2) ◽  
pp. 253-265 ◽  
Author(s):  
S S Macintyre
Keyword(s):  
Binding Site ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Tissue Injury ◽  
Specific Binding ◽  
Phase Response ◽  
C Reactive Protein ◽  
Binding Studies ◽  
Lower Affinity ◽  
Reactive Protein

The half-time for secretion of the plasma protein C-reactive protein (CRP) by the hepatocyte decreases markedly in association with its increased synthesis during the acute phase response to tissue injury (Macintyre, S., D. Samols, and I. Kushner. 1985. J. Biol. Chem. 260:4169-4173). In studies in which subcellular fractions were prepared from cells incubated under pulse-chase conditions, CRP was found to be preferentially retained within the ER of normal hepatocytes, but secreted relatively efficiently in cells prepared from rabbits undergoing the acute phase response. On the basis of the detergent-dependency of specific binding of radiolabeled CRP, as well as EM visualization of biotinylated CRP identified with peroxidase-conjugated streptavidin, CRP was found to bind to the lumenal surface of permeabilized rough microsomes, while no binding was detected in Golgi fractions. As judged by both kinetic and equilibrium binding studies, rough microsomes from control rabbits were found to have two classes of specific binding sites for CRP; a high affinity site (Kd = 1 nM, Bmax = 1 pmol CRP/mg microsomal protein) as well as a much lower affinity (Kd = 140 nM) site. In contrast, only the lower affinity class was detected in microsomes isolated from rabbits undergoing the acute phase response. On nitrocellulose blots probed with radiolabeled CRP a 60-kD protein, distinct from BiP, was detected in extracts of rough microsomes isolated from control rabbits, but not in Golgi fractions or rough microsomes from stimulated animals. These findings correlate with previous observations of changes in secretion kinetics of CRP and are consistent with the hypothesis that the intracellular sorting of CRP could be rerouted by downregulation of a specific ER binding site during the acute phase response.

Acute phase response after myocardial infarction: Correlation between serum levels of cytokines and C-reactive protein

1990 ◽  
Vol 68 (21) ◽  
pp. 1083-1083 ◽  
Author(s):  
H. Tilg ◽  
J. Mair ◽  
M. Herold ◽  
W. E. Aulitzky ◽  
P. Lechleitner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Serum Levels ◽  
Phase Response ◽  
C Reactive Protein ◽  
Reactive Protein

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.

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