Page last updated: 2024-10-24

regulation of leukocyte tethering or rolling

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of leukocyte tethering or rolling. [GO_REF:0000058, GOC:als, GOC:TermGenie, PMID:18308860]

Leukocyte tethering and rolling is a crucial initial step in leukocyte recruitment to sites of inflammation, injury, and infection. This process involves the controlled slowing down and temporary adhesion of leukocytes to the endothelial lining of blood vessels, allowing them to interact with the endothelium and ultimately migrate into the surrounding tissue. This intricate process is mediated by a delicate balance of adhesive and repulsive forces between leukocytes and endothelial cells, primarily orchestrated by specialized molecules known as selectins and chemokines.

**Selectins:**
- **L-selectin** (CD62L) is expressed on leukocytes and binds to GlyCAM-1 and CD34 on endothelial cells.
- **E-selectin** (CD62E) and **P-selectin** (CD62P) are induced on endothelial cells in response to inflammatory signals. These selectins bind to sialyl Lewis X (sLex) and other carbohydrate ligands expressed on leukocytes.

**Chemokines:**
- These small, chemoattractant cytokines are produced by endothelial cells and other cells in response to inflammatory stimuli.
- Chemokines, such as CXCL8 (IL-8), bind to their receptors on leukocytes, triggering intracellular signaling pathways that activate integrins.

**The Rolling Process:**
1. **Initial Tethering:** Weak, transient interactions between L-selectin on leukocytes and GlyCAM-1 or CD34 on endothelial cells initiate the tethering process. This initial interaction slows the leukocyte down.
2. **Rolling Adhesion:** The tethered leukocyte encounters E-selectin or P-selectin expressed on the endothelium. These interactions are weaker than those mediated by integrins, resulting in a rolling motion.
3. **Signal Transduction and Integrin Activation:** As the leukocyte rolls along the endothelial surface, it encounters chemokines. These chemokines bind to receptors on the leukocyte, triggering intracellular signaling cascades that activate integrins.
4. **Firm Adhesion:** Activated integrins, such as LFA-1 and Mac-1 on leukocytes, bind to their ligands, ICAM-1 and ICAM-2, on endothelial cells. This strong adhesion anchors the leukocyte to the endothelium, allowing it to migrate into the surrounding tissue.

**Regulation of Rolling:**
- **Regulation of Selectin Expression:** The expression of E-selectin and P-selectin is tightly regulated by inflammatory signals. This ensures that leukocyte rolling is only initiated when necessary.
- **Chemokine Gradient:** Chemokines act as chemoattractants, creating a concentration gradient that directs leukocyte movement towards the site of inflammation.
- **Integrin Activation:** The activation of integrins is a crucial step in regulating leukocyte adhesion and rolling. This process is regulated by chemokines and other intracellular signaling pathways.

**Conclusion:** Leukocyte tethering and rolling are essential for leukocyte recruitment and are tightly regulated by a complex interplay of selectins, chemokines, and integrins. This sophisticated process ensures that leukocytes are efficiently recruited to sites of inflammation, injury, and infection, while also preventing excessive leukocyte accumulation that could lead to tissue damage.'
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Proteins (2)

ProteinDefinitionTaxonomy
4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase 9A 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase 9 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y231]Homo sapiens (human)
Alpha-(1,3)-fucosyltransferase 7An alpha-(1,3)-fucosyltransferase 7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q11130]Homo sapiens (human)

Compounds (12)

CompoundDefinitionClassesRoles
2,3-dihydroxybenzoic acid2,3-dihydroxybenzoic acid : A dihydroxybenzoic acid that is benzoic acid substituted by hydroxy groups at positions 2 and 3. It occurs naturally in Phyllanthus acidus and in the aquatic fern Salvinia molesta.

2,3-dihydroxybenzoic acid: RN given refers to parent cpd

dihydroxybenzoic acid : Any member of the class of hydroxybenzoic acids carrying two phenolic hydroxy groups on the benzene ring and its derivatives.
dihydroxybenzoic acidhuman xenobiotic metabolite;
plant metabolite
protocatechuic acid3,4-dihydroxybenzoic acid : A dihydroxybenzoic acid in which the hydroxy groups are located at positions 3 and 4.

protocatechuic acid: RN given refers to parent cpd; structure
catechols;
dihydroxybenzoic acid
antineoplastic agent;
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor;
EC 1.14.11.2 (procollagen-proline dioxygenase) inhibitor;
human xenobiotic metabolite;
plant metabolite
gallic acidgallate : A trihydroxybenzoate that is the conjugate base of gallic acid.trihydroxybenzoic acidantineoplastic agent;
antioxidant;
apoptosis inducer;
astringent;
cyclooxygenase 2 inhibitor;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
geroprotector;
human xenobiotic metabolite;
plant metabolite
beta-resorcylic acidbeta-resorcylic acid: RN given refers to parent cpd; structure
2,5-dihydroxybenzoic acid2,5-dihydroxybenzoic acid : A dihydroxybenzoic acid having the two hydroxy groups at the 2- and 5-positions.

2,5-dihydroxybenzoic acid: RN given refers to parent cpd; a oxidative product of saligenin
dihydroxybenzoic acidEC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
fungal metabolite;
human metabolite;
MALDI matrix material;
mouse metabolite
veratric acid3,4-dimethoxybenzoic acid : A member of the class of benzoic acids that is benzoic acid substituted by methoxy groups at positions 2 and 3.

veratric acid: RN given refers to parent cpd; structure
benzoic acidsallergen;
plant metabolite
methyl gallatemethyl 3,4,5-trihydroxybenzoate : A gallate ester obtained by the formal condensation of gallic acid with methanol. It exhibits anti-oxidant, anti-tumor, anti-microbial and anti-inflammatory properties.

methyl gallate: has both immunosuppressive and phytogenic antineoplastic activities; isolated from Acer saccharinum
gallate esteranti-inflammatory agent;
antioxidant;
plant metabolite
3,4,5-trimethoxybenzoic acid3,4,5-trimethoxybenzoic acid : A benzoic acid derivative carrying 3-, 4- and 5-methoxy substituents.

3,4,5-trimethoxybenzoic acid: RN given refers to parent cpd; structure
benzoic acids;
methoxybenzenes
human urinary metabolite;
human xenobiotic metabolite;
plant metabolite
syringic acidsyringic acid : A dimethoxybenzene that is 3,5-dimethyl ether derivative of gallic acid.

syringic acid: RN given refers to parent cpd; structure in third source
benzoic acids;
dimethoxybenzene;
phenols
plant metabolite
epigallocatechin gallate(-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin.

epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis)
flavans;
gallate ester;
polyphenol
antineoplastic agent;
antioxidant;
apoptosis inducer;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent;
plant metabolite
guanosine diphosphateGuanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.guanosine 5'-phosphate;
purine ribonucleoside 5'-diphosphate
Escherichia coli metabolite;
mouse metabolite;
uncoupling protein inhibitor
guanosine triphosphateGuanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.guanosine 5'-phosphate;
purine ribonucleoside 5'-triphosphate
Escherichia coli metabolite;
mouse metabolite;
uncoupling protein inhibitor