Phenotypic and functional change of cytokine-activated neutrophils: inflammatory neutrophils are heterogeneous and enhance adaptive immune responses

Polymorphonuclear leukocytes (PMN) are the most abundant leukocytes, compri sing about two-thirds of peripheral blood leukocytes, and play major roles in innate immunity. In addition, PMN play critical roles in the development of adaptive immunity. Recently, defensins and other peptides pre-stored in PMN granules were shown to attract monocytes, dendritic cells, and T cells , leading to the hypothesis that the release of PMN granular peptides may l ink innate and adaptive immunity. During the past several years, we have fo cused on an alternative hypothesis that activated PMN further differentiate and acquire new phenotypes and functions that enable them to link the two responses. To test our hypothesis, we have taken local and global approache s and have shown several key findings that support the hypothesis. The find ings include the requirement for priming PMN by cytokines to induce the del ayed expression of MCP-1/CCL2, a signal for mononuclear cells, and the expr ession of new cell-surface markers by such cytokine-activated PMN, In the p resent manuscript, we focus on the phenotypic and functional changes that o ccur during PMN activation with selected cytokines, The results of our stud y indicate that inflammatory PMN are heterogeneous and play roles in not on ly innate but also adaptive immunity in response to stimuli released in inj ured tissues.