Acute-phase protein

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Inflammatory cells and red blood cells

Acute-phase proteins (APPs) are a class of

polypeptides
rather than proteins.

In response to

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

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

Positive acute-phase proteins serve (as part of the innate immune system) different physiological functions within the

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
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
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
pattern recognition receptors[8]

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]

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

Measurement of acute-phase proteins, especially C-reactive protein, is a useful marker of inflammation in both medical and veterinary

systemic lupus erythematosus, one may find a raised ESR but normal C-reactive protein.[citation needed]They may also indicate liver failure.[11]


References

  1. ^
    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. PMID 19438602
    .
  4. ISBN 978-0-7817-9543-2
    . Page 182
  5. PMID 7693593
    .
  6. PMID 20711357
    .
  7. PMID 19679815
    .
  8. PMID 11502220
    .
  9. ^
    PMID 10633294
    .
  10. PMID 10627880
    .
  11. PMID 15966220
    .

External links
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