Leukocyte transcellular diapedesis: Rap1b is in control

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Neutrophil transmigration across endothelial barriers is crucial for innate inflammation.
• Neutrophils migrate via paracellular (between cells) or transcellular (through cells) routes.
• Factors determining these distinct migration modes remain largely unknown.

Purpose of the Study:

• To investigate the role of Ras-like Rap1b GTPase in regulating neutrophil transmigration.
• To elucidate the mechanisms by which Rap1b influences paracellular versus transcellular migration.
• To determine the in vivo significance of Rap1b in neutrophil infiltration and inflammatory responses.

Main Methods:

• In vitro assays to assess neutrophil migration modes.
• Molecular analyses of Rap1b and Akt signaling pathways.
• In vivo studies using mouse models of inflammation and endotoxin shock.

Main Results:

• Ras-like Rap1b GTPase was identified as a suppressor of neutrophil transcellular migration.
• Rap1b inhibits transcellular migration by suppressing Akt-driven invasive protrusions.
• Rap1b does not affect paracellular migration and limits neutrophil tissue infiltration in mice.
• Rap1b deficiency leads to increased susceptibility to endotoxin shock.

Conclusions:

• Neutrophil paracellular and transcellular migration are regulated by distinct mechanisms.
• Rap1b GTPase plays a novel inhibitory role in transcellular neutrophil migration and overall inflammation.
• These findings have implications for understanding vascular integrity and innate inflammatory diseases.