Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland
Correspondence: Dr. Joost J. Oppenheim, LMI, DBS, NCI-Frederick, Building 560, Room 21-89, Frederick, MD 21702-1201. E-mail: oppenhei{at}mail.ncifcrf.gov
Defensins and cathelicidins are the two major families of mammalian
anti-microbial proteins. They contribute to host, innate,
anti-microbial defense by disrupting the integrity of the bacterial
cell membrane. However, several members of the mammalian anti-microbial
proteins including defensins and cathelicidins have been shown recently
to have chemotactic effects on host cells. Human neutrophil
-defensins are chemotactic for resting, naïve CD45RA/CD4 T
cells, CD8 T cells, and immature dendritic cells. Human ß-defensins
are also chemotactic for immature dendritic cells but induce the
migration of memory CD45RO/CD4 T cells. In contrast, cathelicidin/LL-37
is chemotactic for neutrophils, monocytes, and T cells but not for
dendritic cells. Thus, these anti-microbial peptides have distinct,
host-target cell spectra. The chemotactic activities of human
ß-defensins and cathelicidin/LL-37 are mediated by human CC chemokine
receptor 6 and formyl peptide receptor-like 1, respectively. The
capacities of defensins and cathelicidins to mobilize various types of
phagocytic leukocytes, immature dendritic cells, and lymphocytes,
together with their other effects such as stimulating IL-8 production
and mast cell degranulation, provide evidence for their participation
in alerting, mobilizing, and amplifying innate and adaptive
anti-microbial immunity of the host.
Key Words: chemotaxis • CCR6 • FPRL1 • phagocytic leukocytes • dendritic cells • keratinocytes • macrophages
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