regulation of neutrophil chemotaxis

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate, or extent of neutrophil chemotaxis. Neutrophil chemotaxis is the directed movement of a neutrophil cell, the most numerous polymorphonuclear leukocyte found in the blood, in response to an external stimulus, usually an infection or wounding. [GOC:dph, GOC:tb]

Neutrophil chemotaxis, the directed migration of neutrophils towards a chemical gradient, is a fundamental process in innate immunity. It involves a complex interplay of signaling pathways, cytoskeletal rearrangements, and adhesion events.

1. **Chemoattractant Sensing and Signal Transduction:**
- Neutrophils express a diverse array of receptors, including G protein-coupled receptors (GPCRs) like formyl peptide receptors (FPRs), chemokine receptors (CXCRs), and complement receptors (CRs), which bind to chemoattractants.
- Binding of chemoattractants to their receptors triggers a signaling cascade involving G proteins, phospholipase C (PLC), diacylglycerol (DAG), inositol triphosphate (IP3), and intracellular calcium release.

2. **Polarization and Directional Migration:**
- The signaling cascade leads to the polarization of the neutrophil, with the leading edge becoming enriched in actin polymerization and the trailing edge enriched in myosin.
- This polarization is driven by the assembly of signaling complexes at the leading edge, including Rac1 and PI3K, which regulate actin polymerization and membrane ruffling.
- Simultaneously, the trailing edge is stabilized by RhoA signaling, promoting actomyosin contraction.

3. **Adhesion and Detachment:**
- Neutrophils adhere to the endothelium via integrins, which are activated by inside-out signaling triggered by chemoattractants.
- This adhesion allows neutrophils to crawl along the vascular wall, following the chemoattractant gradient.
- Detachment from the endothelium is facilitated by the release of matrix metalloproteinases (MMPs), which degrade the extracellular matrix.

4. **Chemotaxis and Resolution:**
- Neutrophils follow the chemoattractant gradient, navigating through tissue and reaching the site of infection or injury.
- Upon reaching the target, neutrophils release antimicrobial peptides, reactive oxygen species, and other inflammatory mediators to fight off pathogens.
- The resolution of the inflammatory response involves the apoptosis of neutrophils and their clearance by macrophages.'
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Proteins (1)

Compounds (12)