Related Experiment Video
Updated: Aug 27, 2025
04:15
Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of β2 Integrin Activation
Published on: February 2, 2024
1.9K
Nexinhib20 Inhibits Neutrophil Adhesion and β2 Integrin Activation by Antagonizing Rac-1-Guanosine 5'-Triphosphate
Wei Liu1, Chunxia G Cronin2, Ziming Cao1
1Department of Immunology, School of Medicine, UConn Health, Farmington, CT.
Journal of Immunology (Baltimore, Md. : 1950)
|September 27, 2022
Summary
Nexinhib20, a novel drug, effectively inhibits neutrophil adhesion and exocytosis. This dual action significantly reduces myocardial ischemia-reperfusion (I/R) injury by limiting neutrophil recruitment and infarct size.
Area of Science:
- Immunology
- Cardiovascular Biology
- Pharmacology
Background:
- Neutrophils play a key role in inflammatory responses.
- Inhibiting neutrophil recruitment is a promising strategy for managing inflammatory injuries like myocardial ischemia-reperfusion (I/R) injury.
- Myocardial I/R injury worsens cardiomyocyte death following acute myocardial infarction treatments.
Purpose of the Study:
- To investigate the dual-functional neutrophil inhibitory effects of Nexinhib20.
- To evaluate Nexinhib20's potential in preventing myocardial I/R injury.
Main Methods:
- Utilized microfluidic chambers to assess IL-8-induced neutrophil adhesion under flow.
- Employed dynamic flow cytometry to analyze intracellular calcium flux and β2 integrin activation.
- Conducted Western blot assays to examine Rac-1 activation and in vitro competition assays to study Rac-1/GTP binding.
- Evaluated Nexinhib20's efficacy in a mouse model of myocardial I/R injury.
Main Results:
- Nexinhib20 inhibited IL-8-induced β2 integrin-dependent neutrophil adhesion under flow.
- Nexinhib20 suppressed intracellular calcium flux and β2 integrin activation.
- Nexinhib20 inhibited Rac-1 activation and antagonized Rac-1/GTP binding.
- Administration of Nexinhib20 post-ischemia and pre-reperfusion significantly reduced neutrophil recruitment and infarct size in a mouse model of myocardial I/R injury.
Conclusions:
- Nexinhib20 acts as a dual-functional inhibitor, targeting both neutrophil exocytosis and adhesion.
- Nexinhib20 demonstrates significant potential for preventing myocardial I/R injury by limiting neutrophil infiltration.
- Nexinhib20 represents a promising therapeutic candidate for mitigating inflammatory damage in cardiovascular conditions.
More Related Videos
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.8K
01:10Integrins
4.1K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
4.1K
01:21Cell Polarization by Rho Proteins
2.8K
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
2.8K
01:24Adherens Junctions
5.0K
Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
Adherens Junctions are Dynamic
5.0K
01:15Activation of Integrins
3.6K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.6K
01:24Small GTPases - Ras and Rho
4.1K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
4.1K