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.
The terms ''acute-phase protein'' and ''acute-phase reactant'' (APR) are often used synonymously, although some APRs are (strictly speaking)
polypeptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
s rather than proteins.
In response to
injury
An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, o ...
, local
inflammatory cells
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
(
neutrophil granulocyte
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
s and
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s) 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.
Regulation of synthesis
TNF-α,
IL-1β and
IFN-γ are important for the expression of inflammatory mediators such as
prostaglandin
The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
s 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 is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
. Cortisol can enhance expression of IL-6
receptors in liver cells and induce IL-6-mediated production of APPs.
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
Mannose-binding lectin (MBL), also called mannan-binding lectin or mannan-binding protein (MBP), is a lectin that is instrumental in innate immunity as an opsonin and via the lectin pathway.
Structure
MBL has an oligomeric structure (400-700 kDa) ...
,
complement factors
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...
,
ferritin,
ceruloplasmin,
serum amyloid A and
haptoglobin. Others give
negative feedback
Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by ...
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.
Also, some products of the coagulation system can contribute to the
innate immune system
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
by their ability to increase vascular permeability and act as
chemotactic agent
Chemotaxis (from ''chemical substance, chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell organism, single-cell or multicellular organisms direct their ...
s for
phagocytic cell
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek ...
s.
Negative
"Negative" acute-phase proteins decrease in inflammation. Examples include
albumin,
,
[ transthyretin,][ 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.
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.
]
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 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
Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
, one may find a raised ESR but normal C-reactive protein.They may also indicate liver failure.
References
External links
* http://eclinpath.com/chemistry/proteins/acute-phase-proteins/
*
{{Authority control
*
Immune system