Neutrophils are the most abundant leukocytes in circulation and play a critical role in innate immunity. In addition, studies using animal disease models strongly suggest their involvement in adaptive immunity. However, the role of neutrophils in adaptive immunity is not clearly understood at the molecular level. We previously demonstrated that cytokine-activated human neutrophils expressed a high level of the CC-chemokine, monocyte chemoattractant protein-1 (MCP-1), and suggested that neutrophil-derived MCP-1 could contribute to the transition from acute to chronic inflammation by attracting monocytes to sites of inflammation. We also showed that neutrophils had the capacity to further mature and express a novel set of genes under appropriate conditions. This year, we have reported that human neutrophils are capable of acquiring new phenotypes, such as CC-chemokine receptor 6, CD83, CD40, and HLA-DR, and associated functions upon activation with cytokines, and activated neutrophils may play a broader role not only in innate immunity but also in adaptive immunity. The fate of leukocytes in a tissue microenvironment is strongly influenced by up- or down-regulation of cell-surface receptor expression, and subsequent interaction of the receptors with their ligands. These ligands include a wide range of agents secreted at the sites and the components of the extracellular matrix (ECM). Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase whose ligand is collagen. We recently detected, for the first time, that peripheral blood mononuclear cells and neutrophils were induced to express DDR1. Functionally, overexpression of the DDR1a isoform in the human monocytic leukemic cell line, THP-1, increased adherence and marked pseudopod formation on collagen-coated plates in a 1-integrin independent manner, and promoted the migration through three-dimensional collagen lattices. Consequently, we have proposed that the interaction of DDR1a with collagen of the ECM results in a requisite intracellular signaling that enables leukocytes to migrate in a tissue microenvironment and participate in host defense.
Showing the most recent 10 out of 18 publications
