17/11/2019 Acute-phase protein - Wikipedia

Acute-phase protein
Acute-phase proteins (APPs) are a class of proteins whose plasma concentrations increase (positive acute-phase
proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-
phase reaction (also called acute-phase response). For acute-phase reaction is characteristic fever, acceleration of
peripherals leukocytes, circulating neutrophils and their precursors.[1] The terms acute-phase protein and acute-phase
reactant (APR) are often used synonymously, although some APRs are (strictly speaking) polypeptides rather than
proteins.

In response to injury, local inflammatory cells (neutrophil granulocytes and macrophages)

secrete a number of cytokines into the bloodstream, most notable of which are the
interleukins IL1, and IL6, and TNFα. The liver responds by producing many acute-phase
reactants. At the same time, the production of a number of other proteins is reduced; these
proteins are, therefore, referred to as "negative" acute-phase reactants. Increased acute-
phase proteins from the liver may also contribute to the promotion of sepsis.[2] Inflammatory cells
and red blood cells

Contents
Regulation of synthesis
Positive
Negative
Clinical significance
See also
References
External links

Regulation of synthesis
TNF-α, IL-1β and INF-γ are important for the expression of inflammatory mediators such as prostagladins and
leukotrienes and they also cause the production of platelet-activating factor and IL-6. After stimulation of
proinflammatory cytokines, Kupffer cells produce IL-6 in the liver and present it to the hepatocytes. IL-6 is the major
mediator for the hepatocytic secretion of APPs. Synthesis of APP can be also regulated indirectly by cortisol. Cortisol
can enhance expression of IL-6 receptors in liver cells and induce IL-6-mediated production of APPs.[1]  

Positive
Positive acute-phase proteins serve (as part of the innate immune system) different physiological functions within the
immune system. Some act to destroy or inhibit growth of microbes, e.g., C-reactive protein, mannose-binding
protein,[3] complement factors, ferritin, ceruloplasmin, serum amyloid A and haptoglobin. Others give negative
feedback on the inflammatory response, e.g. serpins. Alpha 2-macroglobulin and coagulation factors affect coagulation,
mainly stimulating it. This pro-coagulant effect may limit infection by trapping pathogens in local blood clots.[1] Also,
some products of the coagulation system can contribute to the innate immune system by their ability to increase
vascular permeability and act as chemotactic agents for phagocytic cells.

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"Positive" acute-phase proteins:

Protein Immune system function

C-reactive protein Opsonin on microbes[4] (not an acute-phase reactant in mice)

Serum amyloid P
Opsonin
component

Serum amyloid A Recruitment of immune cells to inflammatory sites

Induction of enzymes that degrade extracellular matrix

Complement factors Opsonization, lysis and clumping of target cells. Chemotaxis

Mannan-binding lectin Mannan-binding lectin pathway of complement activation
Fibrinogen, prothrombin,
Coagulation factors, trapping invading microbes in blood clots.
factor VIII,
Some cause chemotaxis
von Willebrand factor

Plasminogen activator Prevents the degradation of blood clots by inhibiting tissue Plasminogen Activator
inhibitor-1 (PAI-1) (tPA) [5]

Alpha 2-macroglobulin Inhibitor of coagulation by inhibiting thrombin.[6]

Inhibitor of fibrinolysis by inhibiting plasmin

Ferritin Binding iron, inhibiting microbe iron uptake [7]

Stimulates the internalization of ferroportin, preventing release of iron bound by
Hepcidin[8]
ferritin within intestinal enterocytes and macrophages
Ceruloplasmin Oxidizes iron, facilitating for ferritin, inhibiting microbe iron uptake
Haptoglobin Binds hemoglobin, inhibiting microbe iron uptake and prevents kidney damage
Orosomucoid
(Alpha-1-acid Steroid carrier
glycoprotein, AGP)
Alpha 1-antitrypsin Serpin, downregulates inflammation
Alpha 1-
Serpin, downregulates inflammation
antichymotrypsin

Negative
"Negative" acute-phase proteins decrease in inflammation. Examples include albumin,[9] transferrin,[9]
transthyretin,[9] retinol-binding protein, antithrombin, transcortin. The decrease of such proteins may be used as
markers of inflammation. The physiological role of decreased synthesis of such proteins is generally to save amino
acids for producing "positive" acute-phase proteins more efficiently. Theoretically, a decrease in transferrin could
additionally be decreased by an upregulation of transferrin receptors, but the latter does not appear to change with
inflammation.[10]

Clinical significance
Measurement of acute-phase proteins, especially C-reactive protein, is a useful marker of inflammation in both
medical and veterinary clinical pathology. It correlates with the erythrocyte sedimentation rate (ESR), however not
always directly. This is due to the ESR being largely dependent on elevation of fibrinogen, an acute phase reactant with
a half-life of approximately one week. This protein will therefore remain higher for longer despite removal of the

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inflammatory stimuli. In contrast, C-reactive protein (with a half-life of 6–8 hours) rises rapidly and can quickly return
to within the normal range if treatment is employed. For example, in active systemic lupus erythematosus, one may
find a raised ESR but normal C-reactive protein.

They may also indicate liver failure.[11]

See also
Wikipedia:MeSH D12.776#MeSH D12.776.124.050 --- acute-phase proteins

References
1. Jain S, Gautam V, Naseem S (January 2011). "Acute-phase proteins: As diagnostic tool" (https://www.ncbi.nlm.ni
h.gov/pmc/articles/PMC3053509). Journal of Pharmacy & Bioallied Sciences. 3 (1): 118–27. doi:10.4103/0975-
7406.76489 (https://doi.org/10.4103%2F0975-7406.76489). PMC 3053509 (https://www.ncbi.nlm.nih.gov/pmc/artic
les/PMC3053509). PMID 21430962 (https://www.ncbi.nlm.nih.gov/pubmed/21430962).
2. Abbas A, Lichtman A, Pillai S (2012). Basic immunology Functions and Disorders of the Immune System (4th ed.).
Philadelphia, PA: Saunders/Elsevier. p. 40.
3. B L Herpers, H Endeman, B A W de Jong, B M de Jongh, J C Grutters, D H Biesma, and H van Velzen-Blad.
Acute-phase responsiveness of mannose-binding lectin in community-acquired pneumonia is highly dependent
upon MBL2 genotypes. Clin Exp Immunol. 2009 Jun;156(3):488-94. PMID 19438602 (https://www.ncbi.nlm.nih.go
v/pubmed/19438602)
4. Lippincott's Illustrated Reviews: Immunology. Paperback: 384 pages. Publisher: Lippincott Williams & Wilkins;
(July 1, 2007). Language: English. ISBN 0-7817-9543-5. ISBN 978-0-7817-9543-2. Page 182
5. Davidson SJ (24 July 2013). "Inflammation and Acute Phase Proteins in Haemostasis". In Janciauskiene S (ed.).
Acute Phase Proteins. doi:10.5772/55998 (https://doi.org/10.5772%2F55998).
6. de Boer JP, Creasey AA, Chang A, Abbink JJ, Roem D, Eerenberg AJ, et al. (December 1993). "Alpha-2-
macroglobulin functions as an inhibitor of fibrinolytic, clotting, and neutrophilic proteinases in sepsis: studies using
a baboon model". Infection and Immunity. 61 (12): 5035–43. PMID 7693593 (https://www.ncbi.nlm.nih.gov/pubme
d/7693593).
7. Koorts AA, Viljoen M (2011). "Acute Phase Proteins: Ferritin and Ferritin Isoforms" (http://cdn.intechopen.com/pdf
s/21451/InTech-Acute_phase_proteins_ferritin_and_ferritin_isoforms.pdf) (PDF). In Veas F (ed.). Acute Phase
Proteins. InTech. doi:10.5772/20586 (https://doi.org/10.5772%2F20586).
8. Vecchi C, Montosi G, Zhang K, et al. (August 2009). "ER stress controls iron metabolism through induction of
hepcidin" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923557). Science. 325 (5942): 877–80.
doi:10.1126/science.1176639 (https://doi.org/10.1126%2Fscience.1176639). PMC 2923557 (https://www.ncbi.nlm.
nih.gov/pmc/articles/PMC2923557). PMID 19679815 (https://www.ncbi.nlm.nih.gov/pubmed/19679815).
9. Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY (1999). "Reference distributions for
the negative acute-phase serum proteins, albumin, transferrin, and transthyretin: a practical, simple and clinically
relevant approach in a large cohort". J. Clin. Lab. Anal. 13 (6): 273–9. doi:10.1002/(SICI)1098-
2825(1999)13:6<273::AID-JCLA4>3.0.CO;2-X (https://doi.org/10.1002%2F%28SICI%291098-2825%281999%291
3%3A6%3C273%3A%3AAID-JCLA4%3E3.0.CO%3B2-X). PMID 10633294 (https://www.ncbi.nlm.nih.gov/pubme
d/10633294).
10. Chua E, Clague JE, Sharma AK, Horan MA, Lombard M (October 1999). "Serum transferrin receptor assay in iron
deficiency anaemia and anaemia of chronic disease in the elderly" (http://qjmed.oxfordjournals.org/content/92/10/5
87.full). QJM. 92 (10): 587–94. doi:10.1093/qjmed/92.10.587 (https://doi.org/10.1093%2Fqjmed%2F92.10.587).
PMID 10627880 (https://www.ncbi.nlm.nih.gov/pubmed/10627880).
11. Ananian P, Hardwigsen J, Bernard D, Le Treut YP (2005). "Serum acute-phase protein level as indicator for liver
failure after liver resection". Hepatogastroenterology. 52 (63): 857–61. PMID 15966220 (https://www.ncbi.nlm.nih.
gov/pubmed/15966220).

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External links
http://eclinpath.com/chemistry/proteins/acute-phase-proteins/
Acute-Phase+Proteins (https://meshb.nlm.nih.gov/record/ui?name=Acute-Phase%20Proteins) at the US National
Library of Medicine Medical Subject Headings (MeSH)

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