Polymorphonuclear neutrophils (PMN) are the most abundant leukocytes and comprise about two-thirds of peripheral blood leukocytes. PMN quickly infiltrate into sites of the inflammatory response upon invasion by pathogens and play an important role in acute inflammation. In addition, several previous reports also suggested that PMN could also be involved in the development of chronic inflammation, including delayed type hypersensitivity (DTH). We previously showed that activation of human PMN with the products of mitogen-activated peripheral blood mononuclear cells resulted in the delayed expression of the CC-chemokine monocyte chemoattractant protein-1 (MCP-1) that regulates infiltration of monocytes, characteristic of the chronic phase of inflammation. We also identified tumor necrosis factor (TNF)-alpha as a key factor. This year we have shown that the delayed expression of MCP-1 appears to be due to a maturation step induced by a 60-kD factor(s), and the mature PMN quickly respond to TNF-alpha for the maximal expression of MCP-1. Thus, our study demonstrated not only high level expression of MCP-1 by PMN, but also the capacity of PMN to further mature under appropriate conditions. To better understand the capacity of cytokine-activated PMN, we investigated a profile of genes expressed by activated PMN using cDNA arrays. Among many genes upregulated in the activated PMN, we focused on the expression of the CC chemokine receptor CCR6 and found that cytokine-activated PMN expressed functional CCR6. Expression of functional CCR6 is of great interest, because CCR6 is highly expressed in immature dendritic cells (DC), suggesting that PMN have the capacity to acquire features characteristic of antigen-presenting DC. In fact, PMN activated with selected cytokines, such as TNF-alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor, expressed CD83, known to be expressed by DC, along with other cell-surface molecules, including CD40 and HLA-DR. Thus, PMN are capable of acquiring new phenotypes and functions upon activation, and activated PMN may play a broader role in not only innate but also adaptive immunity.
Showing the most recent 10 out of 18 publications
