Neutrophils produce biologically active macrophage inflammatory protein-3 alpha (MIP-3 alpha)/CCL20 and MIP-3 beta/CCL19

Macrophage inflammatory protein-3 alpha (MIP-3 alpha)/CCL20 and MIP-3 beta /CCL19 are members of the CC chemokine subfamily which exert their effects through specific receptors, CCR6 and CCR7, respectively. Previously, we hav e reported that human neutrophils have the capacity to produce a number of chemokines, including IL-8/CXCL8, GRO alpha /CXCL1, IP-10/CXCL10, and MIG/C XCL9. Herein, we show that neutrophils also have the ability to express and release MIP-3 alpha /CCL20 and MIP-3 beta /CCL19 when cultured with either LPS or TNF-a. We also report that MIP-3a/CCL20 and MIP-3 beta /CCL19 produ ction by LPS-stimulated neutrophils is negatively modulated by IL-10. Remar kably, we found that supernatants harvested from stimulated neutrophils not only induced chemotaxis of both immature and mature dendritic cells (DC), but also triggered rapid integrin-dependent adhesion of CCR6- and CCR7-expr essing lymphocytes to purified VCAM-1 and ICAM-1, respectively. Importantly , both chemotaxis and rapid integrin-dependent adhesion were dramatically s uppressed by anti-MIP-3 alpha /CCL20 and anti-MIP-3 beta//CCL19 neutralizin g antibodies, indicating that MIP-3 alpha /CCL20 and MIP-3 beta /CCL19 pres ent in the supernatants were both biologically active. As these chemokines are primarily chemotactic for DC and specific lymphocyte subsets, the abili ty of neutrophils to produce MIP-3 alpha /CCL20 and MIP-3 beta /CCL19 might be significant in orchestrating the recruitment of these cell types to the inflamed sites and therefore in contributing to the regulation of the immu ne response.