A myristoylated alanine-rich C-kinase substrate (MARCKS) inhibitor peptide attenuates neutrophil outside-in β ₂ -integrin activation and signaling

MARCKS Inhibition Alters Bovine Neutrophil Responses to Salmonella Typhimurium

“…The finding that MARCKS inhibition attenuated both neutrophil adhesion and migration is consistent with our previously published results. Both adhesion and migration are known to be β 2 -integrin-dependent, and we have previously ascribed a role for MARCKS in neutrophil β 2 -integrin-dependent neutrophil functions [28] and outside-in activation [30,76]. LPS stimulation induces β 2 -integrin-dependent cell spreading [77], reinforcing the likelihood that Salmonella induces β 2 integrin-dependent adhesion.…”

“…Neutrophil adhesion to the vasculature and to the basolateral membrane of the intestine is critical for neutrophil migration into the gut [50,51]. Previous work in our laboratory demonstrated an essential role for MARCKS in neutrophil adhesion [28,30]. Therefore, we hypothesized that MARCKS inhibition in primary bovine neutrophils would decrease STminduced adhesion.…”

“…In addition to cellular actin regulation, MARCKS also has a clear role in inflammatory responses. MARCKS inhibition with N-terminus or phosphorylation-blocking peptides inhibits neutrophil adhesion, migration, ROS production, and pro-inflammatory cytokine production ex vivo [28][29][30][31]. MARCKS-targeting peptides have also been shown to inhibit neutrophils in animal models and human patients in vivo [32][33][34][35][36][37].…”