In
molecular biologyMolecular biology is the study of biology at a molecular level. The field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
,
elastase is an
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
from the class of
proteaseA protease breaks down proteins. A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein...
s (peptidases), that break down
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s.
There exist two human
geneA gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cells and pass genetic traits to offspring...
s for elastase:
- Pancreatic elastase
Pancreatic elastase is a form of elastase formed in the pancreas.From recent research, it appears that of the two, ELA-1 is not transcribed into a protein....
(ELA-1)
- Neutrophil elastase (ELA-2)
Bacterial forms: Organisms such as
P. aeruginosaPseudomonas aeruginosa is a common bacterium which can cause disease in animals and humans. It is found in soil, water, skin flora and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also with little oxygen, and has thus colonised many natural and...
also produce elastase, and is considered a virulence factor.
Elastase breaks down
elastinElastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched...
, an
elasticIn physics, elasticity is the physical property of a material when it returns to its original shape after the stress under which it deforms is removed. The relative amount of deformation is called the strain.- Modelling elasticity :...
fibre that, together with
collagenCollagen is the main protein of connective tissue in animals and the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content. It is naturally found exclusively in metazoa, including sponges. In muscle tissue it serves as a major component of endomysium...
, determines the mechanical properties of
connective tissueConnective tissue is a form of fibrous tissue.. It is one of the four types of tissue in traditional classifications ....
.
In
molecular biologyMolecular biology is the study of biology at a molecular level. The field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
,
elastase is an
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
from the class of
proteaseA protease breaks down proteins. A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein...
s (peptidases), that break down
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s.
Forms and classification
There exist two human
geneA gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cells and pass genetic traits to offspring...
s for elastase:
- Pancreatic elastase
Pancreatic elastase is a form of elastase formed in the pancreas.From recent research, it appears that of the two, ELA-1 is not transcribed into a protein....
(ELA-1)
- Neutrophil elastase (ELA-2)
Bacterial forms: Organisms such as
P. aeruginosaPseudomonas aeruginosa is a common bacterium which can cause disease in animals and humans. It is found in soil, water, skin flora and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also with little oxygen, and has thus colonised many natural and...
also produce elastase, and is considered a virulence factor.
Function
Elastase breaks down
elastinElastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched...
, an
elasticIn physics, elasticity is the physical property of a material when it returns to its original shape after the stress under which it deforms is removed. The relative amount of deformation is called the strain.- Modelling elasticity :...
fibre that, together with
collagenCollagen is the main protein of connective tissue in animals and the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content. It is naturally found exclusively in metazoa, including sponges. In muscle tissue it serves as a major component of endomysium...
, determines the mechanical properties of
connective tissueConnective tissue is a form of fibrous tissue.. It is one of the four types of tissue in traditional classifications ....
. The neutrophil form breaks down the
Outer membrane protein A (OmpA) of
E. coli and other
Gram-negativeGram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
bacteria, and also breaks down
ShigellaShigella is a genus of Gram-negative, non-spore forming rod-shaped bacteria closely related to Escherichia coli and Salmonella. The causative agent of human shigellosis, Shigella cause disease in primates, but not in other mammals. It is only naturally found in humans and apes. During infection,...
virulence factors. This is accomplished through the cleavage of peptide bonds in the target proteins. The specific peptide bonds cleaved are those on the carboxy side of small, hydrophobic amino acids such as
glycineGlycine is an organic compound with the formula NH2CH2COOH. With only a hydrogen atom as its side chain, glycine is the smallest of the 20 amino acids commonly found in proteins....
,
alanineAlanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 proteinogenic amino acids, i.e. the building blocks of proteins. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
, and
valineValine is an α-amino acid with the chemical formula HO
2CCHCH
2.
L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
. For more on how this is accomplished, see
serine proteaseSerine proteases or serine endopeptidases are proteases in which one of the amino acids at the active site is serine....
.
A1AT
Elastase is inhibited by the acute phase protein
α1-antitrypsinAlpha 1-Antitrypsin or α
1-antitrypsin is a glycoprotein and generally known as serum trypsin inhibitor. Alpha 1- antitrypsin is also referred to as alpha-1 proteinase inhibitor because it is a serine protease inhibitor , inhibiting a wide variety of proteases...
(A1AT), which binds almost irreversibly to the active site of elastase and
trypsinTrypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin predominantly cleaves peptide chains at the carboxyl side of the amino acids lysine or arginine, except...
. A1AT is normally secreted by the liver cells into the serum.
α1-antitryspin deficiencyAlpha 1-antitrypsin deficiency is a genetic disorder caused by defective production of alpha 1-antitrypsin , leading to decreased A1AT activity in the blood and lungs, and deposition of excessive abnormal A1AT protein in liver cells. There are several forms and degrees of deficiency...
(A1AD) leads to uninhibited destruction of elastic fiber by elastase; the main result is
pulmonary emphysemaEmphysema is a lung disease, characterized by an abnormal, permanent enlargement of air spaces distal to the terminal bronchioles. The disease is coupled with the destruction of walls, but without obvious fibrosis...
.
Cyclic hematopoeiesis
The
rare diseaseA rare disease, sometimes known as an orphan disease, is any disease that is not common. Typically, a rare disease has such a low prevalence in a population that a physician in a busy general practice would not expect to see more than one case a year....
cyclic hematopoeiesisCyclic neutropenia is a form of neutropenia which tends to occur every three weeks and lasting three to six days at a time due to changing rates of cell production by the bone marrow....
(also called "cyclic neutropenia") is an autosomal dominant
genetic disorderA genetic disorder is an illness caused by abnormalities in genes or chromosomes. While some diseases, such as cancer, are due in part to a genetic disorders, they can also be caused by environmental factors. Most disorders are quite rare and affect one person in every several thousands or millions...
characterised by fluctuating
neutrophil granulocyteThis article is about neutrophils, cells of the immune system. For organisms that grow in neutral pH environments see: Neutrophile.Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of white blood cells in mammals and form an essential part of the innate...
counts over 21-day periods. During
neutropeniaNeutropenia , from Latin prefix neutro- and Greek suffix -πενία is a hematological disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell, in the blood...
, patients are at risk for
infectionAn infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host's resources to multiply, usually at the expense of the host. The infecting organism, or pathogen, interferes with the normal functioning of the...
s. In 1999, this disease was linked to disorders in the ELA-2 gene. Other forms of congenital
neutropeniaNeutropenia , from Latin prefix neutro- and Greek suffix -πενία is a hematological disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell, in the blood...
also appear to be linked to ELA-2 mutations.
Other diseases
Neutrophil elastase is responsible for the blistering in
bullous pemphigoidPemphigoid is a group of uncommon and rare autoimmune blistering skin diseases. As its name indicates, pemphigoid is similar to pemphigus, but unlike pemphigus, pemphigoid does not feature acantholysis....
, a skin condition, in the presence of
antibodiesAntibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses...
.
The role of bacterial elastase in disease
Elastase has been shown to disrupt tight junctions, cause proteolytic damage to tissue, break down cytokines and alpha proteinase inhibitor, cleave
immunoglobulineAntibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses...
A and G (
IgAIga or IGA may stand for:-Places :* Iga, a city in Mie Prefecture, Honshū island, Japan** Iga Ueno Castle, a castle located in the above city...
, IgG), and cleave both C3bi, a component of the
complement systemThe complement system is a biochemical cascade that helps clear pathogens from an organism. It is part of the larger immune system that is not adaptable and does not change over the course of an individual's lifetime; as such it belongs to the innate immune system...
, and CR1, a
receptorIn biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach...
on neutrophils for another complement
moleculeA molecule is defined as an electrically neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds. Molecules are distinguished from polyatomic ions in this strict sense...
involved in
phagocytosisPhagocytosis is the cellular process of phagocytes and protists of engulfing solid particles by the cell membrane to form an internal phagosome...
. The cleavage of IgA, IgG, C3bi, and CR1 contributes to a decrease of the ability of neutrophils to kill
bacteriaThe bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
by phagocytosis. Together all these factors contribute to human
pathologyPathology is the study and diagnosis of disease through examination of organs, tissues, bodily fluids, and whole bodies...
.