beta-Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved.
beta-Defensins are natural peptide antibiotics whose immunomodulatory functions are poorly understood. In the present study, macrophages were found to migrate to human beta-defensins (HBD)-1 to -4 using Galpha(i) proteins as well as MAPK ERK, p38 and JNK as signal transducers. In addition, mast cells responded to HBD-1 to -4 with calcium fluxes as well as chemotaxis, which increased upon stimulation with IgE plus antigen or ionomycin. In contrast, human beta-defensins were unable to induce migration of memory lymphocytes and dendritic cells (DC). Similar to HBD, the murine beta-defensin (mBD)-8 mobilized macrophages and lacked the ability to recruit memory T cells. These findings were unexpected as CCR6 on memory T cells and DC has been previously observed to be a receptor for human beta-defensins. In support of our findings, however, RBL-2H3 as well as 300.19 cells stably expressing CCR6 proved to be unresponsive to HBD-2 and -3. Intriguingly, our observation of a PKC-independent homologous desensitization between HBD-1 to -4 suggests a common receptor for HBD. In summary, chemoattraction of macrophages and mast cells is evolutionary conserved within the beta-defensin family despite a considerable sequence variation and distinct antimicrobial activities. However, CCR6 is not a functional receptor for beta-defensins.
Soruri
Afsaneh
A
Department of Cellular and Molecular Immunology, Georg-August-University Göttingen, Göttingen, Germany.
Grigat
Jasmin
J
Forssmann
Ulf
U
Riggert
Joachim
J
Zwirner
Jörg
J
D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects*; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000378:metabolism; D023083:beta-Defensins / Q000494:pharmacology*
C106311:CCR6 protein, human; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D023083:beta-Defensins; D020928:Mitogen-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go