The role of CEACAMs in neutrophil function.

Abstract

Background: In addition to the long-known antibacterial actions of neutrophils, neutrophils are recognized to have a variety of other effects and are functionally diverse. Neutrophils can either stimulate or inhibit B cells and T cells, regulate NK development and activity, augment or direct the resolution of inflammation, act as myeloid-derived suppressor cells, modulate tumour growth and metastasis and trigger autoimmune diseases. CEACAMs 1, 3, 6 and 8 are expressed on human neutrophils.

Methods: A literature review was performed on the role of CEACAMs in neutrophil function.

Results: CEACAMs 1, 6 and 8 can be upregulated from intracellular stores, while CEACAM3, an opsonin-independent phagocytic receptor, is constitutively expressed. CEACAM1 has an intracellular ITIM motif and an ITSM motif, and CEACAM3 has an ITAM-like motif; CEACAMs 6 and 8 are glycosylphosphatidylinositol-linked. CEACAM8 can also be released in a soluble form. These CEACAMs can interact with multiple other host CEACAMs as well as other molecules on bacteria, fungi and host cells, both transmitting and receiving signals. Known CEACAM-binding pathogens bind the CFG face of the N domain which is also important in CEACAM-CEACAM binding, although the ABDE face also appears to be involved in higher-order oligomers.

Conclusions: Understanding the exact role of each individual CEACAM in human neutrophils is complicated by the fact that the neutrophil CEACAMs can interact with multiple ligands. The data demonstrates some of the many roles of CEACAMs in neutrophil function and the extensive role of the neutrophil in human biology beyond its classical role as a short-lived phagocyte.