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Human Beta Defensin 3 (HBD3) induces migration and activation of antigen presenting cells and acts as an immune enhancer
Author(s) -
Tewary Poonam,
Li Zhenhua,
Rosa Gonzalo,
Chen Qian,
Oppenheim Joost,
Yang De
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.673.10
Subject(s) - microbiology and biotechnology , cd86 , beta defensin , chemotaxis , cd80 , innate immune system , chemistry , immune system , biology , cd40 , immunology , cytotoxic t cell , t cell , in vitro , receptor , biochemistry
Beta Defensins (BDs) are small, cationic peptides, classified by their pattern of conserved cysteines, that are primarily known for their antimicrobial properties. They also act as chemoattractantagents for monocytes and dendritic cells in mammals The best characterized human BDs are HBD1, HBD2, and mouse BD1∼3 (MBD1∼3). HBD1∼2 and MBD2∼3 are chemotactic for immature dendritic cells (iDCs), memory T cells, and mast cells. HBD2 and MBD2 are capable of activating mast cells and DCs. Human β‐defensin 3 (hBD3) is a highly basic 45‐amino‐acid protein that acts both as an antimicrobial agent and as a chemoattractant molecule. The effects of HBD3 and its mouse ortholog, MBD14, on leukocytes are largely uncharacterized to date. Here we report that HBD3 simultaneously acts as a chemoattractant and activator of antigen presenting cells. Using synthetic and recombinant HBD3, we observed that HBD 3 induced migration of CD34 progenitor derived iDCs and CCR6 transfected HEK 293 cells in a dose dependent manner. HBD3 was also chemotactic for human monocytes and was able to induce calcium flux in or by monocytes. HBD3 also induced activation of monocytes by upregulating surface expression of costimulatory molecules like CD40, CD64, CD80, CD86, MHC class II and adhesion molucles like LFA3 and ICAM1. Furthermore HBD3 induced production of IL‐6, IL‐8, IL‐1beta and TNF alpha by monocytes. When injected into mouse peritoneal cavity, HBD3 also caused a marked recruitment of neutrophils and macrophages. Thus, HBD3 appears to be an important mobilizer and activator of innate inflammatory and adaptive immune responses.