Crosslinking of CD66B on peripheral blood neutrophils mediates the release of interleukin-8 from intracellular storage.

Crosslinking of CD66 antigens on the neutrophil surface induces functional responses such as aggregation of the cells and protein kinase activity. Although CD66b (carcinoembryonic antigen-related cell adhesion molecule-8) has been reported as a candidate receptor for galectin-3, its natural ligand is still unknown and therefore its physiologic function remains to be elucidated. We were able to detect the storage of intracellular interleukin-8 (IL-8) in unstimulated human neutrophils and its secretion in response to the crosslinking of CD66b. In contrast to lipopolysaccharide (LPS), the stimulation via CD66b does not induce a de novo synthesis of cytokines but rather a directed release of the preformed IL-8. This process may represent a very low state of activation for the neutrophil. As it extravasates into the tissue, the neutrophil might interact with the extracellular matrix via CD66b. In response to this interaction, polymorphonuclear neutrophils (PMN) release their preformed IL-8, establishing a chemotactic track for other cells to follow. By contact with pathogenic stimuli such as LPS in the infected tissue, the neutrophil then becomes fully activated and is able to synthesize cytokines de novo to release greater quantities.