A cell permeant peptide containing the cytoplasmic tail sequence of Fc receptor type IIA reduces calcium signaling and phagolysosome formation in neutrophils

Receptors for the Fc domain of IgG mediate target recognition, signal transduction, and effector functions including antibody-dependent cytolysis, phagocytosis, and phagolysosome formation. To better understand FcR-mediated functions and to identify potential therapeutic strategies, we employed cell-penetrating (“Trojan”) peptides to deliver “wild-type” (LTL) or modified (AAA) FcγRIIA tail sequences to the neutrophil’s cytoplasm. The Trojan-LTL peptide appeared to label the endoplasmic reticulum whereas the Trojan-AAA peptide distributed throughout the cytoplasm. The Trojan-LTL peptide, but not the Trojan-AAA peptide, decreased Ca2+ signaling at the phagosome and reduced phagolysosome formation. These studies suggest that FcγRIIA’s tail can act as a peptide decoy thereby blunting FcγRIIA-mediated processes, which, in turn, suggests a possible route in managing inflammatory tissue damage.