Previously, we demonstrated that prostaglandin E2 (PGE2) induces C-C chemokine receptor type 7 (CCR7) expression on human monocytes, which stimulates their subsequent migration in response to the CCR7 natural ligands CCL19 and CCL21. In this study, we determined whether PGE2 affects CCR7 expression on macrophages. Flow cytometric analysis and chemotaxis assays were performed on Mono Mac-1-derived macrophage (MDMM-1) as well as unpolarized monocyte-derived macrophages (MDMs) to determine the CCR7 expression and functionality in the presence of PGE2. Data revealed that a MDMM-1 exhibited markedly downregulated CCR7 expression and functionality that were partially restored by treatment with PGE2. In MDMs, we observed a drastic downregulation of CCR7 expression and functionality that were unaffected following PGE2 treatment. Our data indicate that monocyte differentiation induces the loss of CCR7 expression and that PGE2 is unable to modulate CCR7 expression and functionality as shown previously in monocytes. 1. Introduction Monocytes and macrophages orchestrate proper immune responses to pathogens. Monocytes have been demonstrated to be precursors of professional antigen-presenting cells, such as macrophages and dendritic cells (DCs) [1–3]. In response to danger stimuli, circulating blood monocytes migrate into damaged or infected tissues and differentiate into mature macrophages or DCs. After taking up antigens, the activated macrophages and DCs migrate to the draining lymph nodes to present the antigens to T and B cells. Chemokine receptors confer upon cells the ability to detect and move directionally toward a chemotactic stimulus. C-C chemokine receptor type 7 (CCR7) plays a leading role in the mechanism controlling the entry of lymphocytes and mature DCs into lymph nodes. Within lymph nodes, these cells encounter other immune cells for activation, determining the success of cellular immunity after infection [4]. For immature DCs, the maturation process is initiated upon sensing “danger signals” (tissue damage, inflammatory cytokines, or pathogens) [5]; this process occurs concomitantly with their migration from peripheral tissues to the draining lymph nodes. During maturation, CCR7 expression is upregulated, which guides the migratory DCs to the lymph nodes [6–8]. The chemokines CCL19 and CCL21 are the natural ligands of CCR7, and they are expressed by lymphatic endothelium and/or within lymph nodes by stromal cells, endothelial cells, and DCs [9–13]. Mice deficient in CCL19, CCL21, or CCR7 demonstrate defective DC trafficking and altered immune
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