Page last updated: 2024-10-24

regulation of neutrophil apoptotic process

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate, or extent of neutrophil apoptotic process. [GOC:add, GOC:mtg_apoptosis]

Regulation of neutrophil apoptotic process is a tightly controlled mechanism that ensures proper immune function and prevents excessive inflammation. Neutrophils, a type of white blood cell, are crucial for fighting infections but have a short lifespan and must undergo programmed cell death (apoptosis) to avoid causing tissue damage. This process involves a delicate balance between pro-apoptotic and anti-apoptotic signals, ultimately leading to the dismantling of the cell without triggering inflammatory responses.

**Pro-Apoptotic Signals:**

* **Reactive Oxygen Species (ROS):** Neutrophils produce ROS during phagocytosis and other immune responses. Excessive ROS accumulation triggers apoptotic pathways.
* **Cytokines:** TNF-alpha, IFN-gamma, and IL-10 are cytokines that promote neutrophil apoptosis.
* **Growth Factor Deprivation:** The absence of survival factors like granulocyte colony-stimulating factor (G-CSF) can induce apoptosis.
* **DNA Damage:** Exposure to damaging agents like radiation or certain chemicals can activate DNA repair mechanisms, but persistent DNA damage can trigger apoptosis.

**Apoptotic Pathway Activation:**

* **Caspase Cascade:** Pro-apoptotic signals activate caspases, a family of cysteine proteases, through a cascade. Caspase-8 and caspase-9 are key initiators, while caspase-3 is a key executioner that cleaves cellular proteins, leading to cell dismantling.
* **Mitochondrial Pathway:** The release of cytochrome c from mitochondria into the cytoplasm activates caspase-9 and the apoptotic cascade. This release is regulated by the balance between pro- and anti-apoptotic proteins like Bcl-2 family members.
* **Death Receptor Pathway:** Engagement of death receptors (e.g., Fas, TRAIL-R1/2) on the neutrophil surface by their ligands triggers caspase-8 activation and the apoptotic cascade.

**Anti-Apoptotic Signals:**

* **Survival Factors:** G-CSF, IL-3, and GM-CSF are cytokines that inhibit apoptosis by activating survival pathways.
* **Anti-Apoptotic Proteins:** Proteins like Bcl-2 and Bcl-xL prevent cytochrome c release from mitochondria, blocking the mitochondrial pathway.
* **Apoptosis Inhibitors:** Some cells produce inhibitors of caspases, delaying or preventing apoptosis.

**Consequences of Dysregulation:**

* **Excessive Neutrophil Survival:** Can lead to prolonged inflammation, tissue damage, and autoimmune diseases.
* **Premature Neutrophil Apoptosis:** May impair immune response and increase susceptibility to infections.

**Regulation of Neutrophil Apoptosis is essential for maintaining a balanced immune response, preventing excessive inflammation, and ensuring efficient clearance of pathogens.'
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Proteins (1)

ProteinDefinitionTaxonomy
Cystine/glutamate transporterA cystine/glutamate transporter that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UPY5]Homo sapiens (human)

Compounds (9)

CompoundDefinitionClassesRoles
mesalaminemesalamine : A monohydroxybenzoic acid that is salicylic acid substituted by an amino group at the 5-position.

Mesalamine: An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed)
amino acid;
aromatic amine;
monocarboxylic acid;
monohydroxybenzoic acid;
phenols
non-steroidal anti-inflammatory drug
sulfapyridinesulfapyridine : A sulfonamide consisting of pyridine with a 4-aminobenzenesulfonamido group at the 2-position.

Sulfapyridine: Antibacterial, potentially toxic, used to treat certain skin diseases.
pyridines;
substituted aniline;
sulfonamide;
sulfonamide antibiotic
antiinfective agent;
dermatologic drug;
drug allergen;
environmental contaminant;
xenobiotic
sulfasalazinesulfasalazine : An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4'-position.

Sulfasalazine: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)
cysteinecysteine;
cysteine zwitterion;
L-alpha-amino acid;
proteinogenic amino acid;
serine family amino acid
EC 4.3.1.3 (histidine ammonia-lyase) inhibitor;
flour treatment agent;
human metabolite
quisqualic acidQuisqualic Acid: An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis.non-proteinogenic alpha-amino acid
serine o-sulfateL-serine O-sulfate : A non-proteinogenic L-alpha-amino acid that is the O-sulfo derivative of L-serine.

serine O-sulfate: RN given refers to (L)-isomer
L-serine derivative;
non-proteinogenic L-alpha-amino acid;
O-sulfoamino acid
homocysteic acidhomocysteic acid : A non-proteinogenic alpha-amino acid that is homocysteine in which the thiol group has benn oxidised to the corresponding sulfonic acid.

homocysteic acid: promotes growth in hypophysectomized rats; RN given refers to parent cpd

L-homocysteic acid : A homocysteic acid with L-configuration.
homocysteic acidNMDA receptor agonist
susalimodsusalimod: analogue of sulphasalazine, was designed for use in the treatment of rheumatoid arthritis
erastinerastin : A member of the class of quinazolines that is quinazolin-4(3H)-one in which the hydrogens at positions 2 and 3 are replaced by 1-{4-[(4-chlorophenoxy)acetyl]piperazin-1-yl}ethyl and 2-ethoxyphenyl groups, respectively. It is an inhibitor of voltage-dependent anion-selective channels (VDAC2 and VDAC3) and a potent ferroptosis inducer.

erastin: an antineoplastic agent; structure in first source
aromatic ether;
diether;
monochlorobenzenes;
N-acylpiperazine;
N-alkylpiperazine;
quinazolines;
tertiary carboxamide
antineoplastic agent;
ferroptosis inducer;
voltage-dependent anion channel inhibitor