Serum amyloid A (SAA) proteins are a family of

apolipoprotein Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fats, cholesterol and fat soluble vitamins) to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph. The lipid components of lipoproteins ...

s associated with

high-density lipoprotein High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...

(HDL) in plasma. Different isoforms of SAA are expressed constitutively (constitutive SAAs) at different levels or in response to inflammatory stimuli (

acute phase 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- ...

SAAs). These proteins are produced predominantly by the liver.

Acute-phase serum amyloid A proteins

Acute-phase serum amyloid A proteins (A-SAAs) are secreted during the acute phase of

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

. These proteins have several roles, including the transport of

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...

to the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

for secretion into the

bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bi ...

, the recruitment of immune cells to inflammatory sites, and the induction of

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

s that degrade

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...

. A-SAAs are implicated in several chronic inflammatory diseases, such as

amyloidosis Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weig ...

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...

, and

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...

. Three acute-phase SAA

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some is ...

s have been reported in mice, called

SAA1 Serum amyloid A1 (SAA1) is a protein that in humans is encoded by the ''SAA1'' gene. SAA1 is a major acute-phase protein mainly produced by hepatocytes in response to infection, tissue injury and malignancy. When released into blood circulation, SA ...

SAA2 Serum amyloid A protein is a protein that in humans is encoded by the ''SAA2'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ...

, and SAA3. During

, SAA1 and SAA2 are expressed and induced principally in the

, whereas SAA3 is induced in many distinct tissues. SAA1 and SAA2 genes are regulated in liver cells by the proinflammatory

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...

s IL-1, IL-6, and TNF-α. Both SAA1 and SAA2 are induced up to a 1000-fold in mice under acute inflammatory conditions following exposure to bacterial

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O- antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the out ...

(LPS). Three A-SAA genes have also been identified in humans, although the third

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

, ''SAA3'', is believed to represent a

pseudogene Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes ar ...

that does not generate

messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

. Molecular weights of the human proteins are estimated at 11.7 kDa for SAA1 and 12.8 kDa for SAA4. Serum amyloid A (SAA) is also an acute phase marker that responds rapidly. Similar to CRP, levels of acute-phase SAA increase within hours after inflammatory stimulus, and the magnitude of increase may be greater than that of CRP. Relatively trivial inflammatory stimuli can lead to SAA responses. It has been suggested that SAA levels correlate better with disease activity in early inflammatory joint disease than do ESR and CRP. Although largely produced by hepatocytes, more recent studies show that SAA is produced by adipocytes as well, and its serum concentration is associated with

body mass index Body mass index (BMI) is a value derived from the mass ( weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and ...

Constitutive serum amyloid A proteins

A fourth SAA (SAA4) was identified in humans and is expressed constitutively in the liver and, thus, is defined as a constitutive SAA (C-SAA). A similar protein that is now also called SAA4 has since been identified in the mouse; it had originally been designated SAA5.

References

{{Amyloidosis Amyloidosis Immune system Acute-phase proteins