Nexinhib20 inhibits JFC1-mediated mobilization of a subset of CD11b/CD18+ vesicles decreasing integrin avidity, but does not inhibit Rac1.

ABSTRACT: Regulated sequential exocytosis of neutrophil granules is essential for orchestrating the innate immune response, while uncontrolled secretion causes inflammation. We developed and characterized Nexinhib20, a small-molecule inhibitor that targets azurophilic granule exocytosis in neutrophils by blocking the interaction between the small GTPase Rab27a and its effector JFC1. Its therapeutic potential has been demonstrated in several preclinical models of inflammatory disease. Here, using neutrophils from Jfc1-KO mice, we show that JFC1 regulates the mobilization of a small subpopulation of CD11b+ granules. Nexinhib20 inhibits the mobilization of β2-integrins from a subset of CD11b+ granules to the plasma membrane in human and mouse neutrophils. The putative impact of Nexinhib20 on integrin a

SUBMITTER: Askari K 

PROVIDER: S-EPMC12022635 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature