Eosinophil cationic protein
Encyclopedia
Eosinophil Cationic Protein (ECP) also known as ribonuclease 3 is a basic protein located in the eosinophil primary matrix. In humans, the eosinophil cationic protein is encoded by the RNASE3 gene
.
ECP is released during degranulation of eosinophils. This protein is related to inflammation and asthma because in these cases, there are increased levels of ECP in the body.
There are three glycosolated
forms of ECP and consequently ECP has a range of molecular weights from 18-22 kDa.
are both members of the ribonuclease
superfamily. Both proteins possess neurotoxic, helmintho
-toxic, and ribonucleo
-lytic activities. Eosinophil cationic protein is localized to the granule
matrix of the eosinophil.
When the two known ribonuclease active-site residues to non-functional counterparts (Lysine at position 38 to Arginine and Histidine at position 128 to Aspartate) and were compared it to the wild-type ECP. The mutated ECP retains its cytotoxicity but no longer has its ribonuclease activity. The experiment confirmed that converting the two amino acids to non-functional counter parts did inhibit ECP’s ribonuclease activity. However, ECP retained it anti-parasitic activity. Also, it did not change the production and transportation of ECP in bacteria.
ECP is a potent cytotoxic protein capable of killing cells of guinea pig tracheal epithelium, mammalian leukemia, epidermis carcinoma, and breast carcinoma, as well as non-mammalian cells such as parasites, bacteria, and viruses.
Mature ECP is cytotoxic to human bronchial epithelial (BEAS-2B) cells by specific binding to cell surface heparan sulfate proteoglycans (HSPGs) followed by endocytosis.
ECP triggers apoptosis by caspase-8 activation through mitochondria-independent pathway. Increases in chromatin condensation, sub-G1 population, PARP cleavage, and DNA fragmentation indicate that ECP induces apoptosis in human bronchial epithelial (BEAS-2B) cells.
s appear in large numbers in inflammation sites and in response to certain parasitic infections. These cytoplasmic granulocytes contain positively charged proteins that characterize the cells. ECP is one of the four highly basic proteins that enter the surrounding tissues when activated eosinophil degranulate. Although circulating ECP levels can vary widely among patients, some studies show that serum ECP measurements are useful in monitoring many active inflammatory diseases. ECP concentrations in plasma and other body fluids increase during inflammatory reactions are marked by activated eosinophils.
Serum ECP levels has also been thought as a useful, objective measurement for asthma severity. Increased ECP levels correspond to symptom onset. In seasonal asthmatic patients, ECP measurement reflected changes in disease activity throughout the year.
There are several mechanisms that can be combined to generate an asthma
attack, including specific IgE
antibodies, activated inflammatory cells, neurogenic mechanisms, hyperresponsiveness and individual hormonal imbalances. Allergic reactions in the lung typically have two phases, in which the late phase typically occur several hours after exposure, in which eosinophils accumulate in the bronchus
and resease granule proteins that causes bronchial irritability. ECP is also toxic to neurons, some epithelial cell lines and isolated myocardinal cells. This could be a reason for itching disorders of the skin in patients.
Serum ECP concentrations has also been linked to atopic dermatitis
(AD) activity. ECP correlates with the symptoms (lichenification, Sleep deprivation
, erythema
, papules, pruritus and excoriations) for AD and also correlates with the total clinical score.
Serum ECP measurement for assessing asthma severity, monitoring therapy and indicating severity of certain inflammatory skin conditions present an advantage over subjective clinical measures that are prone to inconsistencies due to broad variability of individual investigator and patient assessments, especially in young children.
The normal reference range for blood tests for eosinophil cationic protein is between 2.3 and 16 µg/L.
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
ECP is released during degranulation of eosinophils. This protein is related to inflammation and asthma because in these cases, there are increased levels of ECP in the body.
There are three glycosolated
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
forms of ECP and consequently ECP has a range of molecular weights from 18-22 kDa.
Function
Eosinophil cationic protein and the sequence related eosinophil-derived neurotoxinEosinophil-derived neurotoxin
Non-secretory ribonuclease is an enzyme that in humans is encoded by the RNASE2 gene.The protein encoded by this gene is found in eosinophil granulocytes.-Further reading:-External links:...
are both members of the ribonuclease
Ribonuclease
Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...
superfamily. Both proteins possess neurotoxic, helmintho
Parasitic worm
Parasitic worms or helminths are a division of eukaryoticparasites that, unlike external parasites such as lice and fleas, live inside their host. They are worm-like organisms that live and feed off living hosts, receiving nourishment and protection while disrupting their hosts' nutrient...
-toxic, and ribonucleo
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
-lytic activities. Eosinophil cationic protein is localized to the granule
Granule
Granule is a generic term used for a small particle or grain. The generic term is employed in a variety of specific contexts.* Granule , visible structures in the photosphere of the Sun arising from activity in the Sun's convective zone...
matrix of the eosinophil.
Ribonuclease activity and cytotoxicity
The ribonuclease activity of ECP is not essential for cytotoxicity.When the two known ribonuclease active-site residues to non-functional counterparts (Lysine at position 38 to Arginine and Histidine at position 128 to Aspartate) and were compared it to the wild-type ECP. The mutated ECP retains its cytotoxicity but no longer has its ribonuclease activity. The experiment confirmed that converting the two amino acids to non-functional counter parts did inhibit ECP’s ribonuclease activity. However, ECP retained it anti-parasitic activity. Also, it did not change the production and transportation of ECP in bacteria.
ECP is a potent cytotoxic protein capable of killing cells of guinea pig tracheal epithelium, mammalian leukemia, epidermis carcinoma, and breast carcinoma, as well as non-mammalian cells such as parasites, bacteria, and viruses.
Mature ECP is cytotoxic to human bronchial epithelial (BEAS-2B) cells by specific binding to cell surface heparan sulfate proteoglycans (HSPGs) followed by endocytosis.
ECP-induced apoptosis
Studies show that ECP, along with other RNases including EDN, had been reported to induce apoptosis in cells. A latest study indicated that ECP caused cytotoxicity in HL-60 and HeLa cells via caspase-3 like activity. Accordingly, cytotoxic RNases play an important role in cell death. However, the mechanism of ECP-induced apoptosis is still not fully verified. Recent studies have shown that eosinophils can induce epithelial cell death via apoptosis and necrosis.ECP triggers apoptosis by caspase-8 activation through mitochondria-independent pathway. Increases in chromatin condensation, sub-G1 population, PARP cleavage, and DNA fragmentation indicate that ECP induces apoptosis in human bronchial epithelial (BEAS-2B) cells.
Clinical significance
Eosinophil granulocyteEosinophil granulocyte
Eosinophil granulocytes, usually called eosinophils or eosinophiles , are white blood cells that are one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells, they also control mechanisms associated with...
s appear in large numbers in inflammation sites and in response to certain parasitic infections. These cytoplasmic granulocytes contain positively charged proteins that characterize the cells. ECP is one of the four highly basic proteins that enter the surrounding tissues when activated eosinophil degranulate. Although circulating ECP levels can vary widely among patients, some studies show that serum ECP measurements are useful in monitoring many active inflammatory diseases. ECP concentrations in plasma and other body fluids increase during inflammatory reactions are marked by activated eosinophils.
Serum ECP levels has also been thought as a useful, objective measurement for asthma severity. Increased ECP levels correspond to symptom onset. In seasonal asthmatic patients, ECP measurement reflected changes in disease activity throughout the year.
There are several mechanisms that can be combined to generate an asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
attack, including specific IgE
IGE
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...
antibodies, activated inflammatory cells, neurogenic mechanisms, hyperresponsiveness and individual hormonal imbalances. Allergic reactions in the lung typically have two phases, in which the late phase typically occur several hours after exposure, in which eosinophils accumulate in the bronchus
Bronchus
A bronchus is a passage of airway in the respiratory tract that conducts air into the lungs. The bronchus branches into smaller tubes, which in turn become bronchioles....
and resease granule proteins that causes bronchial irritability. ECP is also toxic to neurons, some epithelial cell lines and isolated myocardinal cells. This could be a reason for itching disorders of the skin in patients.
Serum ECP concentrations has also been linked to atopic dermatitis
Atopic dermatitis
Atopic dermatitis is an inflammatory, chronically relapsing, non-contagious and pruritic skin disorder...
(AD) activity. ECP correlates with the symptoms (lichenification, Sleep deprivation
Sleep deprivation
Sleep deprivation is the condition of not having enough sleep; it can be either chronic or acute. A chronic sleep-restricted state can cause fatigue, daytime sleepiness, clumsiness and weight loss or weight gain. It adversely affects the brain and cognitive function. Few studies have compared the...
, erythema
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
, papules, pruritus and excoriations) for AD and also correlates with the total clinical score.
Serum ECP measurement for assessing asthma severity, monitoring therapy and indicating severity of certain inflammatory skin conditions present an advantage over subjective clinical measures that are prone to inconsistencies due to broad variability of individual investigator and patient assessments, especially in young children.
The normal reference range for blood tests for eosinophil cationic protein is between 2.3 and 16 µg/L.