positive regulation of leukocyte mediated cytotoxicity
Definition
Target type: biologicalprocess
Any process that activates or increases the frequency, rate or extent of leukocyte mediated cytotoxicity. [GOC:add, ISBN:0781735149, PMID:11911826]
Positive regulation of leukocyte mediated cytotoxicity is a complex biological process involving the coordinated action of various immune cells and signaling pathways to effectively target and eliminate infected or cancerous cells. It plays a crucial role in maintaining immune homeostasis and protecting the host from pathogens and malignant cells.
The process begins with the recognition of target cells by leukocytes, primarily cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. These immune cells express specific receptors, including T cell receptors (TCRs) and NK cell receptors, that bind to antigens presented on the surface of target cells.
Once a target cell is identified, a cascade of signaling events is triggered within the leukocyte, leading to the activation of cytotoxic mechanisms. The key signaling pathways involved include the TCR signaling pathway in CTLs and the NK cell receptor signaling pathway in NK cells.
In CTLs, the TCR recognizes and binds to antigen-MHC complexes presented on target cells, initiating a signaling cascade that activates intracellular kinases, transcription factors, and effector molecules. This signaling pathway culminates in the production of cytotoxic proteins, such as perforin and granzyme, which are stored in specialized secretory granules within CTLs.
NK cells, on the other hand, use a variety of receptors to identify and target cells that lack MHC I expression or express stress-induced ligands. The activation of NK cell receptors triggers signaling pathways that lead to the release of cytotoxic granules containing perforin and granzyme.
Perforin, a pore-forming protein, inserts into the cell membrane of the target cell, creating pores that allow granzyme to enter the cell. Granzyme is a serine protease that triggers apoptosis, or programmed cell death, in the target cell by activating caspase cascades, which ultimately dismantle the cell's structure and lead to its demise.
In addition to cytotoxic granules, CTLs and NK cells can also employ other mechanisms to eliminate target cells. These include the expression of Fas ligand (FasL), which binds to Fas receptor on target cells, triggering the apoptosis pathway.
Overall, positive regulation of leukocyte mediated cytotoxicity involves a multifaceted interplay of recognition, signaling, and effector mechanisms that ensure the precise and efficient elimination of target cells, contributing to the maintenance of immune homeostasis and the protection of the host from disease.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Nitric oxide synthase, inducible | A nitric oxide synthase, inducible that is encoded in the genome of human. [PRO:WCB, UniProtKB:P35228] | Homo sapiens (human) |
Compounds (34)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| n-(3-(aminomethyl)benzyl)acetamidine | N-(3-(aminomethyl)benzyl)acetamidine: structure in first source N-[3-(aminomethyl)benzyl]acetamidine : An aralkylamine that is Nbenzylacetamidine substituted at position 3 on the benzene ring by an aminomethyl group. An inhibitor of nitric oxide synthase. | aralkylamine; carboxamidine; primary amino compound | angiogenesis inhibitor; EC 1.14.13.39 (nitric oxide synthase) inhibitor; geroprotector |
| 2-amino-4-picoline | 2-amino-4-picoline: RN given refers to parent cpd | ||
| 3-bromo-7-nitroindazole | |||
| 7-nitroindazole | 7-nitroindazole: an inhibitor of nitric oxide synthase; exhibits anti-nociceptive activity without increasing blood pressure | ||
| pimagedine | aminoguanidine : A one-carbon compound whose unique structure renders it capable of acting as a derivative of hydrazine, guanidine or formamide. pimagedine: diamine oxidase & nitric oxide synthase inhibitor; an advanced glycosylation end product inhibitor; used in the treatment of diabetic complications; structure | guanidines; one-carbon compound | EC 1.14.13.39 (nitric oxide synthase) inhibitor; EC 1.4.3.4 (monoamine oxidase) inhibitor |
| guanethidine | guanethidine : A member of the class of guanidines in which one of the hydrogens of the amino group has been replaced by a 2-azocan-1-ylethyl group. guanethidine sulfate : A organic sulfate salt composed of two molecules of guanethidine and one of sulfuric acid. Guanethidine: An antihypertensive agent that acts by inhibiting selectively transmission in post-ganglionic adrenergic nerves. It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues. | azocanes; guanidines | adrenergic antagonist; antihypertensive agent; sympatholytic agent |
| etiron | etiron: a nitric oxide synthase inhibitor; RN given refers to parent cpd; structure | ||
| s-methylisothiopseudouronium | S-methylisothiopseudouronium: inhibits nitric oxide synthase; structure in first source | ||
| arginine | arginine : An alpha-amino acid that is glycine in which the alpha-is substituted by a 3-guanidinopropyl group. Arginine: An essential amino acid that is physiologically active in the L-form. | arginine; glutamine family amino acid; L-alpha-amino acid; proteinogenic amino acid | biomarker; Escherichia coli metabolite; micronutrient; mouse metabolite; nutraceutical |
| alpha-aminopyridine | alpha-aminopyridine: RN given refers to parent cpd; structure in Merck Index, 9th ed, #485 aminopyridine : Compounds containing a pyridine skeleton substituted by one or more amine groups. | ||
| oleanolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | plant metabolite | |
| 1,2-Dihydroquinolin-2-imine | aminoquinoline | ||
| 2-amino-3-methylpyridine | 2-amino-3-methylpyridine: structure in first source | ||
| 2-aminothiazoline | 2-aminothiazoline: RN given refers to parent cpd; structure in first source & in Negwer, 5th ed, #97 4,5-dihydro-1,3-thiazol-2-amine : A 1,3-thiazole that is 4,5-dihydro-1,3-thiazole substituted by an amino group at position 2. | 1,3-thiazoles; primary amino compound | |
| guanoxan | guanoxan: was MH 1976-92 (see under GUANIDINES 1976-90); use GUANIDINES to search GUANOXAN 1976-92; antihypertensive agent similar in its mechanism of action to guanethidine; may cause liver damage | benzodioxine | |
| guanadrel | guanadrel : A spiroketal resulting from the formal condensation of the keto group of cyclohexanone with the hydroxy groups of 1-(2,3-dihydroxypropyl)guanidine. A postganglionic adrenergic blocking agent formerly used (generally as the sulfate salt) for the management of hypertension, it has been largely superseded by other drugs less likely to cause orthostatic hypotension (dizzy spells on standing up or stretching). guanadrel: RN given refers to parent cpd; structure | guanidines; spiroketal | adrenergic antagonist; antihypertensive agent |
| ng-nitroarginine methyl ester | NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension. | alpha-amino acid ester; L-arginine derivative; methyl ester; N-nitro compound | EC 1.14.13.39 (nitric oxide synthase) inhibitor |
| 1-aminoisoquinoline | |||
| s-methylthiocitrulline | S-methyl-L-thiocitrulline : An L-arginine derivative in which the guanidino NH2 group of L-arginine is replaced by a methylsufanyl group. S-methylthiocitrulline: a nitric oxide synthase inhibitor; structure in first source | imidothiocarbamic ester; L-arginine derivative; L-ornithine derivative; non-proteinogenic L-alpha-amino acid | EC 1.14.13.39 (nitric oxide synthase) inhibitor; neuroprotective agent |
| n(g)-iminoethylornithine | L-alpha-amino acid | ||
| n(omega)-hydroxyarginine | N(5)-[(Z)-amino(hydroxyimino)methyl]-L-ornithine : An N(5)-[amino(hydroxyimino)methyl]-L-ornithine in which the double bond has Z-configuration. N(omega)-hydroxyarginine: can cause vasorelaxation of bovine intrapulmonary artery; structure given in first source | amino acid zwitterion; N(5)-[(E)-amino(hydroxyimino)methyl]ornithine; N(5)-[(hydroxyamino)(imino)methyl]ornithine; N(5)-[(Z)-amino(hydroxyimino)methyl]ornithine; N(5)-[amino(hydroxyimino)methyl]-L-ornithine; N(5)-[amino(hydroxyimino)methyl]ornithine; N(omega)-hydroxy-L-arginine | |
| omega-n-methylarginine | N(omega)-methyl-L-arginine : A L-arginine derivative with a N(omega)-methyl substituent. omega-N-Methylarginine: A competitive inhibitor of nitric oxide synthetase. | amino acid zwitterion; arginine derivative; guanidines; L-arginine derivative; non-proteinogenic L-alpha-amino acid | |
| ng-nitroarginine methyl ester | N(gamma)-nitro-L-arginine methyl ester hydrochloride : A hydrochloride obtained by combining N(gamma)-nitro-L-arginine methyl ester with one equivalent of hydrochloric acid. | hydrochloride | EC 1.14.13.39 (nitric oxide synthase) inhibitor |
| delta-n-methylarginine | N(5)-methyl-L-arginine : A non-proteinogenic L-alpha-amino acid that is L-arginine substituted by a methyl group at N(5)-position. | guanidines; L-arginine derivative; non-proteinogenic L-alpha-amino acid | |
| 2-amino-5,6-dihydro-4h-1,3-thiazine | 2-amino-5,6-dihydro-4H-1,3-thiazine: RN given refers to parent cpd | ||
| Bardoxolone | cyclohexenones | ||
| canavanine | L-canavanine : A non-proteinogenic L-alpha-amino acid that is L-homoserine substituted at oxygen with a guanidino (carbamimidamido) group. Although structurally related to L-arginine, it is non-proteinogenic. | amino acid zwitterion; non-proteinogenic L-alpha-amino acid | phytogenic insecticide; plant metabolite |
| nitroarginine | N(gamma)-nitro-L-arginine : An L-arginine derivative that is L-arginine in which the terminal nitrogen of the guanidyl group is replaced by a nitro group. Nitroarginine: An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6) | guanidines; L-arginine derivative; N-nitro compound; non-proteinogenic L-alpha-amino acid | |
| arl 17477 | |||
| n(6)-(1-iminoethyl)lysine | N(6)-acetimidoyl-L-lysine : An L-lysine derivative that is L-lysine in which one of the hydrogens attached to N(6) is substituted by an acetimidoyl group | L-lysine derivative; non-proteinogenic L-alpha-amino acid | |
| gw 274150 | |||
| aq4n | AQ4N: structure given in first source | ||
| oleanonic acid | oleanonic acid: structure in first source | ||
| n-trans-p-coumaroyl-l-tyrosine | N-trans-p-coumaroyl-L-tyrosine: from Theobroma cacao; structure in first source | tyrosine derivative |