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)

Compounds (12)