In molecular biology, elastase is an enzyme from the class of proteases (peptidases), that break down proteins.
Forms and classification
There exist two human
genes for elastase:
Bacterial forms: Organisms such as P. aeruginosa also produce elastase, and is considered a virulence factor.
Function
Elastase breaks down
elastin, an
elastic fiber that, together with
collagen, determines the mechanical properties of
connective tissue. The neutrophil form breaks down the
Outer membrane protein A (OmpA) of
E. coli and other
Gram-negative bacteria, and also breaks down
Shigella 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
glycine,
alanine, and
valine. For more on how this is accomplished, see
serine protease.
The role of human elastase in disease
A1AT
Elastase is inhibited by the
acute phase protein
α1-antitrypsin (A1AT), which binds almost irreversibly to the active site of elastase and
trypsin. A1AT is normally secreted by the liver cells into the serum.
α1-antitryspin deficiency (A1AD) leads to uninhibited destruction of elastic fiber by elastase; the main result is
pulmonary emphysema.
Cyclic hematopoeiesis
The
rare disease cyclic hematopoeiesis (also called "cyclic neutropenia") is an
autosomal dominant genetic disorder characterised by fluctuating
neutrophil granulocyte counts over 21-day periods. During
neutropenia, patients are at risk for
infections. In
1999, this disease was linked to disorders in the ELA-2 gene. Other forms of congenital
neutropenia also appear to be linked to ELA-2 mutations.
Other diseases
Neutrophil elastase is responsible for the blistering in
bullous pemphigoid, a skin condition, in the presence of
antibodies.
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
immunoglobuline A and G (
IgA,
IgG), and cleave both C3bi, a component of the
complement system, and CR1, a
receptor on
neutrophils for another complement
molecule involved in
phagocytosis. The cleavage of IgA, IgG, C3bi, and CR1 contributes to a decrease of the ability of
neutrophils to kill
bacteria by phagocytosis. Together all these factors contribute to human
pathology.
References
