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Acute-phase protein

January 01, 1970

Acute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either 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). The acute-phase reaction characteristically involves fever, acceleration of peripheral 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.

Inflammatory cells and red blood cells

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 TNF-α. 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]

Regulation of synthesis edit

TNF-α, IL-1β and IFN-γ are important for the expression of inflammatory mediators such as prostaglandins and leukotrienes, and they also cause the production of platelet-activating factor and IL-6. After stimulation with 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 also be 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 edit

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.[citation needed]

"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 component Opsonin
Serum amyloid A
Complement factors Opsonization, lysis and clumping of target cells. Chemotaxis
Mannan-binding lectin Mannan-binding lectin pathway of complement activation
Fibrinogen, prothrombin, factor VIII,
von Willebrand factor 		Coagulation factors, trapping invading microbes in blood clots.
Some cause chemotaxis
Plasminogen activator inhibitor-1 (PAI-1) Prevents the degradation of blood clots by inhibiting tissue Plasminogen Activator (tPA)
Alpha 2-macroglobulin
Ferritin Binding iron, inhibiting microbe iron uptake[6]
Hepcidin[7] Stimulates the internalization of ferroportin, preventing release of iron bound by 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 glycoprotein, AGP) 		Steroid carrier
Alpha 1-antitrypsin Serpin, downregulates inflammation
Alpha 1-antichymotrypsin Serpin, downregulates inflammation
Lipopolysaccharide binding protein (LBP) Attaches to bacterial LPS, evoke immune responses via pattern recognition receptors[8]

Negative edit

"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]

While the production of C3 (a complement factor) increases in the liver, the plasma concentration often lowers because of an increased turn-over, therefore it is often seen as a negative acute-phase protein.[citation needed]

Clinical significance edit

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 the elevation of fibrinogen, an acute phase reactant with a half-life of approximately one week. This protein will therefore remain higher for longer despite the removal of the 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.[citation needed]They may also indicate liver failure.[11]


References edit

  1. ^ a b c Jain S, Gautam V, Naseem S (January 2011). "Acute-phase proteins: As diagnostic tool". Journal of Pharmacy & Bioallied Sciences. 3 (1): 118–27. doi:10.4103/0975-7406.76489. PMC 3053509. PMID 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. ^ Herpers BL, Endeman H, de Jong BA, de Jongh BM, Grutters JC, Biesma DH, van Velzen-Blad H (Jun 2009). "Acute-phase responsiveness of mannose-binding lectin in community-acquired pneumonia is highly dependent upon MBL2 genotypes". Clin Exp Immunol. 156 (3): 488–94. doi:10.1111/j.1365-2249.2009.03929.x. PMC 2691978. PMID 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. ^ 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. doi:10.1128/iai.61.12.5035-5043.1993. PMC 281280. PMID 7693593.
  6. ^ Skaar EP (2010). "The battle for iron between bacterial pathogens and their vertebrate hosts". PLOS Pathog. 6 (8): e1000949. doi:10.1371/journal.ppat.1000949. PMC 2920840. PMID 20711357.
  7. ^ Vecchi C, Montosi G, Zhang K, et al. (August 2009). "ER stress controls iron metabolism through induction of hepcidin". Science. 325 (5942): 877–80. Bibcode:2009Sci...325..877V. doi:10.1126/science.1176639. PMC 2923557. PMID 19679815.
  8. ^ Muta T, Takeshige K (2001). "Essential roles of CD14 and lipopolysaccharide-binding protein for activation of toll-like receptor (TLR)2 as well as TLR4 Reconstitution of TLR2- and TLR4-activation by distinguishable ligands in LPS preparations". Eur. J. Biochem. 268 (16): 4580–9. doi:10.1046/j.1432-1327.2001.02385.x. PMID 11502220.
  9. ^ a b c 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. PMC 6808097. PMID 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". QJM. 92 (10): 587–94. doi:10.1093/qjmed/92.10.587. PMID 10627880.
  11. ^ Ananian P, Hartvigsen 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.

External links edit

January 01, 1970
acute, phase, protein, apps, class, proteins, whose, concentrations, blood, plasma, either, increase, positive, acute, phase, proteins, decrease, negative, acute, phase, proteins, response, inflammation, this, response, called, acute, phase, reaction, also, ca. Acute phase proteins APPs are a class of proteins whose concentrations in blood plasma either 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 The acute phase reaction characteristically involves fever acceleration of peripheral 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 Inflammatory cells and red blood cells 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 TNF a 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 Contents 1 Regulation of synthesis 2 Positive 3 Negative 4 Clinical significance 5 References 6 External linksRegulation of synthesis editTNF a IL 1b and IFN g are important for the expression of inflammatory mediators such as prostaglandins and leukotrienes and they also cause the production of platelet activating factor and IL 6 After stimulation with 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 also be 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 editPositive 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 citation needed 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 component Opsonin 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 factor VIII von Willebrand factor Coagulation factors trapping invading microbes in blood clots Some cause chemotaxis Plasminogen activator inhibitor 1 PAI 1 Prevents the degradation of blood clots by inhibiting tissue Plasminogen Activator tPA Alpha 2 macroglobulin Inhibitor of coagulation by inhibiting thrombin 5 Inhibitor of fibrinolysis by inhibiting plasmin Ferritin Binding iron inhibiting microbe iron uptake 6 Hepcidin 7 Stimulates the internalization of ferroportin preventing release of iron bound by 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 glycoprotein AGP Steroid carrier Alpha 1 antitrypsin Serpin downregulates inflammation Alpha 1 antichymotrypsin Serpin downregulates inflammation Lipopolysaccharide binding protein LBP Attaches to bacterial LPS evoke immune responses via pattern recognition receptors 8 Negative edit 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 While the production of C3 a complement factor increases in the liver the plasma concentration often lowers because of an increased turn over therefore it is often seen as a negative acute phase protein citation needed Clinical significance editMeasurement 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 the elevation of fibrinogen an acute phase reactant with a half life of approximately one week This protein will therefore remain higher for longer despite the removal of the 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 citation needed They may also indicate liver failure 11 References edit a b c Jain S Gautam V Naseem S January 2011 Acute phase proteins As diagnostic tool Journal of Pharmacy amp Bioallied Sciences 3 1 118 27 doi 10 4103 0975 7406 76489 PMC 3053509 PMID 21430962 Abbas A Lichtman A Pillai S 2012 Basic immunology Functions and Disorders of the Immune System 4th ed Philadelphia PA Saunders Elsevier p 40 Herpers BL Endeman H de Jong BA de Jongh BM Grutters JC Biesma DH van Velzen Blad H Jun 2009 Acute phase responsiveness of mannose binding lectin in community acquired pneumonia is highly dependent upon MBL2 genotypes Clin Exp Immunol 156 3 488 94 doi 10 1111 j 1365 2249 2009 03929 x PMC 2691978 PMID 19438602 Lippincott s Illustrated Reviews Immunology Paperback 384 pages Publisher Lippincott Williams amp Wilkins July 1 2007 Language English ISBN 0 7817 9543 5 ISBN 978 0 7817 9543 2 Page 182 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 doi 10 1128 iai 61 12 5035 5043 1993 PMC 281280 PMID 7693593 Skaar EP 2010 The battle for iron between bacterial pathogens and their vertebrate hosts PLOS Pathog 6 8 e1000949 doi 10 1371 journal ppat 1000949 PMC 2920840 PMID 20711357 Vecchi C Montosi G Zhang K et al August 2009 ER stress controls iron metabolism through induction of hepcidin Science 325 5942 877 80 Bibcode 2009Sci 325 877V doi 10 1126 science 1176639 PMC 2923557 PMID 19679815 Muta T Takeshige K 2001 Essential roles of CD14 and lipopolysaccharide binding protein for activation of toll like receptor TLR 2 as well as TLR4 Reconstitution of TLR2 and TLR4 activation by distinguishable ligands in LPS preparations Eur J Biochem 268 16 4580 9 doi 10 1046 j 1432 1327 2001 02385 x PMID 11502220 a b c 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 lt 273 AID JCLA4 gt 3 0 CO 2 X PMC 6808097 PMID 10633294 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 QJM 92 10 587 94 doi 10 1093 qjmed 92 10 587 PMID 10627880 Ananian P Hartvigsen 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 External links edithttp eclinpath com chemistry proteins acute phase proteins Acute Phase Proteins at the U S National Library of Medicine Medical Subject Headings MeSH Portals nbsp Biology nbsp Medicine Retrieved from https en wikipedia org w index php title Acute phase protein amp oldid 1191597818, wikipedia, wiki, book, books, library,

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