Neutrophil elastase (, ''leukocyte elastase'', ''ELANE'', ''ELA2'', ''elastase 2'', ''neutrophil'', ''elaszym'', ''serine elastase'', subtype ''human leukocyte elastase (HLE)'') is a serine

proteinase A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurri ...

in the same family as chymotrypsin and has broad substrate specificity. Neutrophil

elastase In molecular biology, elastase is an enzyme from the class of ''proteases (peptidases)'' that break down proteins. In particular, it is a serine protease. Forms and classification Eight human genes exist for elastase: Some bacteria (includin ...

is secreted by

neutrophil 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 during inflammation, and destroys

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

and host tissue. It also localizes to

neutrophil extracellular traps Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens. Neutrophils are the immune system's first line of defense against infection and have conventionally be ...

(NETs), via its high affinity for DNA, an unusual property for serine proteases. As with other serine proteinases it contains a charge relay system composed of the

catalytic triad A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, li ...

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the d ...

, aspartate, and serine residues that are dispersed throughout the primary sequence of the polypeptide but that are brought together in the three dimensional conformation of the folded protein. The gene encoding neutrophil elastase, ELA2, consists of five exons. Neutrophil elastase is closely related to other cytotoxic immune serine proteases, such as the granzymes and

cathepsin G Cathepsin G is a protein that in humans is encoded by the ''CTSG'' gene. It is one of the three serine proteases of the chymotrypsin family that are stored in the azurophil granules, and also a member of the peptidase S1 protein family. Cathepsin ...

. It is more distantly related to the digestive

CELA1 Chymotrypsin-like elastase family member 1 (CELA1) also known as elastase-1 (ELA1) is an enzyme that in humans is encoded by the CELA1 gene. Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans ...

. The neutrophil form of elastase () is 218

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s long, with two

asparagine Asparagine (symbol Asn or N) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...

-linked

carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...

chains (see '' glycosylation''). It is present in

azurophil An azurophilic granule is a cellular object readily stainable with a Romanowsky stain. In white blood cells and hyperchromatin, staining imparts a burgundy or merlot coloration. Neutrophils in particular are known for containing azurophils load ...

granules in the neutrophil

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

. There appear to be two forms of neutrophil elastase, termed IIa and IIb.

Gene

In humans, neutrophil elastase is encoded by the ''ELANE''

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 ba ...

, which resides on chromosome 19.

Function

Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes that encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Neutrophil elastase hydrolyzes proteins within specialized neutrophil lysosomes, called

azurophil granules An azurophilic granule is a cellular object readily stainable with a Romanowsky stain. In white blood cells and hyperchromatin, staining imparts a burgundy or merlot coloration. Neutrophils in particular are known for containing azurophils l ...

, as well as proteins of the extracellular matrix following the protein's release from activated neutrophils. Neutrophil elastase may play a role in degenerative and inflammatory diseases by its proteolysis of collagen-IV and elastin of the extracellular matrix. This protein degrades the outer membrane protein A (OmpA) of E. coli as well as the virulence factors of such bacteria as Shigella, Salmonella and Yersinia. Mutations in this gene are associated with

cyclic neutropenia Cyclic neutropenia (CyN) is a rare hematologic disorder and form of congenital neutropenia that tends to occur approximately every three weeks and lasting for few days at a time due to changing rates of neutrophil production by the bone marrow. It ...

(CyN) and

severe congenital neutropenia Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations. SCN manifests in ...

(SCN). At least 95 disease-causing mutations in this gene have been discovered. This gene is clustered with other serine protease gene family members, azurocidin 1 and proteinase 3 genes, at chromosome 19pter. All 3 genes are expressed coordinately and their protein products are packaged together into

during neutrophil differentiation.

Clinical significance

Neutrophil elastase is an important protease enzyme that when expressed aberrantly can cause

emphysema Emphysema, or pulmonary emphysema, is a lower respiratory tract disease, characterised by air-filled spaces ( pneumatoses) in the lungs, that can vary in size and may be very large. The spaces are caused by the breakdown of the walls of the alve ...

or emphysematous changes. This involves breakdown of the lung structure and increased airspaces. Mutations of the ''ELANE'' gene cause

cyclic Cycle, cycles, or cyclic may refer to: Anthropology and social sciences * Cyclic history, a theory of history * Cyclical theory, a theory of American political history associated with Arthur Schlesinger, Sr. * Social cycle, various cycles in s ...

and severe congenital

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...

, which is a failure of neutrophils to mature. In 2019 study was confirmed that ''ELANE'' deletion does not cause neutropenia.

Inhibitors

In order to minimize damage to tissues, there are few inhibitors of neutrophil elastase. One group of inhibitors are the

Serpin Serpins are a Protein superfamily, superfamily of proteins with similar structures that were first identified for their Protease inhibitor (biology), protease inhibition activity and are found in all kingdom (biology), kingdoms of life. The acr ...

s (Serine Protease Inhibitors). Neutrophil elastase has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

Alpha 2-antiplasmin Alpha 2-antiplasmin (or α2-antiplasmin or plasmin inhibitor) is a serine protease inhibitor (serpin) responsible for inactivating plasmin. Plasmin is an important enzyme that participates in fibrinolysis and degradation of various other protein ...

, which belongs to the Serpin family of proteins.

References

External links

GeneReviews/NCBI/NIH/UW entry on ELANE-Related Neutropenias
* * {{Portal bar, Biology, border=no EC 3.4.21 Extracellular matrix remodeling enzymes