DE YANG - Academia.edu (original) (raw)

Papers by DE YANG

Journal of Leukocyte Biology, 2006

High mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays a criti... more High mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays a critical role in regulating gene transcription. Recently, HMGB1 has also been shown to act as a late mediator of endotoxic shock and to exert a variety of proinflammatory, extracellular activities. Here, we report that HMGB1 simultaneously acts as a chemoattractant and activator of dendritic cells (DCs). HMGB1 induced the migration of monocyte-derived, immature DCs (Mo-iDCs) but not mature DCs. The chemotactic effect of HMGB1 on iDCs was pertussis toxin-inhibitable and also inhibited by antibody against the receptor of advanced glycation end products (RAGE), suggesting that HMGB1 chemoattraction of iDCs is mediated by RAGE in a Gi protein-dependent manner. In addition, HMGB1 treatment of Mo-iDCs up-regulated DC surface markers (CD80, CD83, CD86, and HLA-A,B,C), enhanced DC production of cytokines (IL-6, CXCL8, IL-12p70, and TNF-␣), switched DC chemokine responsiveness from CCL5-sensitive to CCL21-sensitive, and acquired the capacity to stimulate allogeneic T cell proliferation. Based on its dual DC-attracting and -activating activities as well as its reported capacity to promote an antigen-specific immune response, we consider HMGB1 to have the properties of an immune alarmin. J. Leukoc. Biol. 81: 59 -66; 2007.

We have previously shown that antimicrobial peptides like defensins have the capacity to mobilize... more We have previously shown that antimicrobial peptides like defensins have the capacity to mobilize leukocytes in host defense. LL-37 is the cleaved antimicrobial 37-residue, COOH-terminal peptide of hCAP18 (human cationic antimicrobial protein with a molecular size of 18 kD), the only identified member in humans of a family of proteins called cathelicidins. LL-37/ hCAP18 is produced by neutrophils and various epithelial cells. Here we report that LL-37 is chemotactic for, and can induce Ca 2 ϩ mobilization in, human monocytes and formyl peptide receptor-like 1 (FPRL1)-transfected human embryonic kidney 293 cells. LL-37-induced Ca 2 ϩ mobilization in monocytes can also be cross-desensitized by an FPRL1-specific agonist. Furthermore, LL-37 is also chemotactic for human neutrophils and T lymphocytes that are known to express FPRL1. Our results suggest that, in addition to its microbicidal activity, LL-37 may contribute to innate and adaptive immunity by recruiting neutrophils, monocytes, and T cells to sites of microbial invasion by interacting with FPRL1.

Immunological Reviews, 2000

"... It is likely that the leukocyte granulations are in fact secretory products, which ... more "... It is likely that the leukocyte granulations are in fact secretory products, which the cell dissolves and spreads to the environment as needed", Paul Ehrlich, 1900. Neutrophil granules have long been recognized as mediators of innate host defense. Newly discovered functions for individual granule proteins suggest that granule constituents may also participate in adaptive immune responses. Neutrophil granule-derived cathepsin G, azurocidin/CAP37 and alpha-defensins have been shown to be chemotactic for mononuclear cells and neutrophils. Analysis of the chemotactic activity of alpha-defensins shows that they induce CD45RA+ and CD8 T-lymphocyte cell migration at concentrations 10 to 100-fold below that required for direct bactericidal activity. Additionally, alpha and beta defensins form chemotactic gradients for immature dendritic cells. Recruiting immature dendritic cells to sites of infection is one way for neutrophil granule proteins to initiate adaptive immune responses. Granules found in other leukocytes such as mast cells also contain serine proteases, such as chymase, that are known to chemoattract neutrophils and mononuclear cells. Preliminary evidence suggests that exocytosis of granule-derived products from a variety of leukocytes can mobilize inflammatory cells and immunocytes. Thus, leukocyte granule-derived proteins, more rapidly than chemokines, can mobilize cells that mediate innate host defense and adaptive immunity.

Defensins and cathelicidins are the two major families of mammalian anti-microbial proteins. They... more 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 ␤-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 ␤-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. J. Leukoc. Biol. 69: 691-697; 2001.

Proceedings of The National Academy of Sciences, 2003

Human defensins form a family of small, cationic, and Cys-rich antimicrobial proteins that play i... more Human defensins form a family of small, cationic, and Cys-rich antimicrobial proteins that play important roles in innate immunity against invading microbes. They also function as effective immune modulators in adaptive immunity by selectively chemoattracting T lymphocytes and immature dendritic cells. On the basis of sequence homology and the connectivity of six conserved Cys residues, human defensins are classified into ␣ and ␤ families. Structures of several ␤-defensins have recently been characterized, confirming the disulfide connectivity conserved within the family, i.e., Cys 1 -Cys 5 , Cys 2 -Cys 4 , and Cys 3 -Cys 6 . We found that human ␤-defensin 3 (hBD3), a recently described member of the growing ␤ family, did not fold preferentially into a native conformation in vitro under various oxidative conditions. Using the orthogonal protection of Cys 1 -Cys 5 and of Cys 1 -Cys 6 , we chemically synthesized six topological analogs of hBD3 with predefined disulfide connectivities, including the (presumably) native ␤ pairing. Unexpectedly, all differently folded hBD3 species exhibited similar antimicrobial activity against Escherichia coli, whereas a wide range of chemotactic activities was observed with these analogs for monocytes and cells transfected by the chemokine receptor CCR6. Furthermore, whereas substitution of all Cys residues by ␣-aminobutyric acid completely abolished the chemotactic activity of hBD3, the bactericidal activity remained unaffected in the absence of any disulfide bridge. Our findings demonstrate that disulfide bonding in hBD3, although required for binding and activation of receptors for chemotaxis, is fully dispensable for its antimicrobial function, thus shedding light on the mechanisms of action for human ␤-defensins and the design of novel peptide antibiotics.

Current Opinion in Immunology, 2005

Trends in Immunology, 2002

Mammalian defensins are small, cationic, antimicrobial peptides encoded by the host that are cons... more Mammalian defensins are small, cationic, antimicrobial peptides encoded by the host that are considered to be important antibiotic-like effectors of innate immunity. By using chemokine receptors on dendritic cells and T cells, defensins might also contribute to the regulation of host adaptive immunity against microbial invasion. Defensins have considerable immunological adjuvant activity and linkage of β β-defensins or selected chemokines to an idiotypic lymphoma antigen has yielded potent antitumor vaccines. The functional overlap between defensins and chemokines is reinforced by reports that some chemokines have antimicrobial activities. Although showing similarity in activity and overall tertiary structure, the evolutionary relationship between defensins and chemokines remains to be determined.

Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucy... more Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucyl-, or threonyl-tRNA synthetase occur in ‫ف‬ 25% of patients with polymyositis or dermatomyositis. We tested the ability of several aminoacyl-tRNA synthetases to induce leukocyte migration. HisRS induced CD4 ϩ and CD8 ϩ lymphocytes, interleukin (IL)-2-activated monocytes, and immature dendritic cells (iDCs) to migrate, but not neutrophils, mature DCs, or unstimulated monocytes. An NH 2 -terminal domain, 1-48 HisRS, was chemotactic for lymphocytes and activated monocytes, whereas a deletion mutant, HisRS-M, was inactive. HisRS selectively activated CC chemokine receptor (CCR)5-transfected HEK-293 cells, inducing migration by interacting with extracellular domain three. Furthermore, monoclonal anti-CCR5 blocked HisRS-induced chemotaxis and conversely, HisRS blocked anti-CCR5 binding. Asparaginyl-tRNA synthetase induced migration of lymphocytes, activated monocytes, iDCs, and CCR3-transfected HEK-293 cells. Seryl-tRNA synthetase induced migration of CCR3-transfected cells but not iDCs. Nonautoantigenic aspartyl-tRNA and lysyl-tRNA synthetases were not chemotactic. Thus, autoantigenic aminoacyl-tRNA synthetases, perhaps liberated from damaged muscle cells, may perpetuate the development of myositis by recruiting mononuclear cells that induce innate and adaptive immune responses. Therefore, the selection of a self-molecule as a target for an autoantibody response may be a consequence of the proinflammatory properties of the molecule itself.

Journal of Leukocyte Biology, 2003

Previous studies have demonstrated that ␤-defensins exhibit chemotactic activity by sharing the c... more Previous studies have demonstrated that ␤-defensins exhibit chemotactic activity by sharing the chemokine receptor CCR6 with the CC chemokine ligand CCL20/macrophage-inflammatory protein-3␣ (MIP-3␣). Structural analysis of CCL20/MIP-3␣ revealed that most of the positively charged residues are concentrated at one area of its topological surface, a characteristic considered to be important for the antimicrobial activity of defensins. Here, we report that similar to defensins, CCL20/MIP-3␣ has antimicrobial effects on Escherichia coli, Pseudomonas aeruginosa, Moraxella catarrhalis, Streptococcus pyogenes, Enterococcus faecium, Staphylococcus aureus, and Candida albicans. Additionally, by screening a total of 30 human chemokines, we have identified an additional 17 human chemokines, which exhibit antimicrobial activity in vitro. Collectively, about two-thirds of the chemokines investigated so far has the capacity to kill microorganisms in vitro, suggesting that antimicrobial activity may be another host-defense function for certain chemokines. Comparison of the structural characteristics between antimicrobial and nonantimicrobial chemokines suggests that topological formation of a large, positively charged electrostatic patch on the surface of the molecule is likely to be a common structural feature of antimicrobial chemokines. J. Leukoc. Biol. 74: 448 -455; 2003.

Defensins, a family of cationic, structurally related, antimicrobial peptides, contribute to host... more Defensins, a family of cationic, structurally related, antimicrobial peptides, contribute to host defense by disrupting the cytoplasmic membrane of microbes. Here we show that human neutrophil defensins selectively induce the migration of human CD4 ؉ /CD45RA ؉ naive and CD8 ؉ , but not CD4 ؉ /CD45RO ؉ memory, T cells. Moreover, human neutrophil defensins are chemotactic for immature human dendritic cells derived from either CD34 ؉ progenitors or peripheral blood monocytes. Upon maturation induced by treatment with tumor necrosis factor ␣ (TNF-␣), dendritic cells lose their responsiveness to human neutrophil defensins. The chemotactic effect of human neutrophil defensins on both T and dendritic cells is pertussis toxin-sensitive, suggesting that a G i␣ protein-coupled receptor is responsible. Human neutrophil defensins are also chemotactic for immature murine dendritic cells. These data suggest that, in addition to their antimicrobial role, human neutrophil defensins also contribute to adaptive immunity by mobilizing T cells and dendritic cells.

Annual Review of Immunology, 2004

Mammals generate a diverse array of antimicrobial proteins, largely represented by defensins or c... more Mammals generate a diverse array of antimicrobial proteins, largely represented by defensins or cathelicidins. The direct in vitro microbicidal activity of antimicrobial proteins has long been considered an important innate immune defense, although the in vivo relevance has only very recently been established for certain defensins and cathelicidins. Mammalian defensins and cathelicidins have also been shown to have multiple receptor-mediated effects on immune cells. Beta-defensins interact with CCR6; murine beta-defensin-2 in addition activates TLR4. Cathelicidins act on FPRL1-expressing cells. Furthermore, several defensins have considerable immunoenhancing activity. Thus, it appears that mammalian antimicrobial proteins contribute to both innate and adaptive antimicrobial immunity.

The impact of health communication is generally enhanced when it is targeted or tailored to the n... more The impact of health communication is generally enhanced when it is targeted or tailored to the needs of a specific population or individual. In a segmentation analysis of the U.S adult population-using data from 2,636 respondents to a mail panel survey-we identified four segments of the adult population that vary significantly with regard to health information preferences based on their degree of engagement in health enhancement, and their degree of independence in health decision making. We also created a brief (10 item), easy-to-administer screening instrument that indicates into which segment people fall. The purpose of this article is to describe the segments, and the screening instrument, and to present initial tests of its validity. We believe this instrument offers a practical tool for differentiating motivationally coherent subgroups of the adult population with regard to their health information preferences, and therefore may have practical value in improving health communication and health services provision efforts. Additional research is needed to further validate the tool and test its utility in guiding the creation of targeted health messages and programs.

Journal of Leukocyte Biology, 2006

High mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays a criti... more High mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays a critical role in regulating gene transcription. Recently, HMGB1 has also been shown to act as a late mediator of endotoxic shock and to exert a variety of proinflammatory, extracellular activities. Here, we report that HMGB1 simultaneously acts as a chemoattractant and activator of dendritic cells (DCs). HMGB1 induced the migration of monocyte-derived, immature DCs (Mo-iDCs) but not mature DCs. The chemotactic effect of HMGB1 on iDCs was pertussis toxin-inhibitable and also inhibited by antibody against the receptor of advanced glycation end products (RAGE), suggesting that HMGB1 chemoattraction of iDCs is mediated by RAGE in a Gi protein-dependent manner. In addition, HMGB1 treatment of Mo-iDCs up-regulated DC surface markers (CD80, CD83, CD86, and HLA-A,B,C), enhanced DC production of cytokines (IL-6, CXCL8, IL-12p70, and TNF-␣), switched DC chemokine responsiveness from CCL5-sensitive to CCL21-sensitive, and acquired the capacity to stimulate allogeneic T cell proliferation. Based on its dual DC-attracting and -activating activities as well as its reported capacity to promote an antigen-specific immune response, we consider HMGB1 to have the properties of an immune alarmin. J. Leukoc. Biol. 81: 59 -66; 2007.

We have previously shown that antimicrobial peptides like defensins have the capacity to mobilize... more We have previously shown that antimicrobial peptides like defensins have the capacity to mobilize leukocytes in host defense. LL-37 is the cleaved antimicrobial 37-residue, COOH-terminal peptide of hCAP18 (human cationic antimicrobial protein with a molecular size of 18 kD), the only identified member in humans of a family of proteins called cathelicidins. LL-37/ hCAP18 is produced by neutrophils and various epithelial cells. Here we report that LL-37 is chemotactic for, and can induce Ca 2 ϩ mobilization in, human monocytes and formyl peptide receptor-like 1 (FPRL1)-transfected human embryonic kidney 293 cells. LL-37-induced Ca 2 ϩ mobilization in monocytes can also be cross-desensitized by an FPRL1-specific agonist. Furthermore, LL-37 is also chemotactic for human neutrophils and T lymphocytes that are known to express FPRL1. Our results suggest that, in addition to its microbicidal activity, LL-37 may contribute to innate and adaptive immunity by recruiting neutrophils, monocytes, and T cells to sites of microbial invasion by interacting with FPRL1.

Immunological Reviews, 2000

"... It is likely that the leukocyte granulations are in fact secretory products, which ... more "... It is likely that the leukocyte granulations are in fact secretory products, which the cell dissolves and spreads to the environment as needed", Paul Ehrlich, 1900. Neutrophil granules have long been recognized as mediators of innate host defense. Newly discovered functions for individual granule proteins suggest that granule constituents may also participate in adaptive immune responses. Neutrophil granule-derived cathepsin G, azurocidin/CAP37 and alpha-defensins have been shown to be chemotactic for mononuclear cells and neutrophils. Analysis of the chemotactic activity of alpha-defensins shows that they induce CD45RA+ and CD8 T-lymphocyte cell migration at concentrations 10 to 100-fold below that required for direct bactericidal activity. Additionally, alpha and beta defensins form chemotactic gradients for immature dendritic cells. Recruiting immature dendritic cells to sites of infection is one way for neutrophil granule proteins to initiate adaptive immune responses. Granules found in other leukocytes such as mast cells also contain serine proteases, such as chymase, that are known to chemoattract neutrophils and mononuclear cells. Preliminary evidence suggests that exocytosis of granule-derived products from a variety of leukocytes can mobilize inflammatory cells and immunocytes. Thus, leukocyte granule-derived proteins, more rapidly than chemokines, can mobilize cells that mediate innate host defense and adaptive immunity.

Defensins and cathelicidins are the two major families of mammalian anti-microbial proteins. They... more 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 ␤-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 ␤-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. J. Leukoc. Biol. 69: 691-697; 2001.

Proceedings of The National Academy of Sciences, 2003

Human defensins form a family of small, cationic, and Cys-rich antimicrobial proteins that play i... more Human defensins form a family of small, cationic, and Cys-rich antimicrobial proteins that play important roles in innate immunity against invading microbes. They also function as effective immune modulators in adaptive immunity by selectively chemoattracting T lymphocytes and immature dendritic cells. On the basis of sequence homology and the connectivity of six conserved Cys residues, human defensins are classified into ␣ and ␤ families. Structures of several ␤-defensins have recently been characterized, confirming the disulfide connectivity conserved within the family, i.e., Cys 1 -Cys 5 , Cys 2 -Cys 4 , and Cys 3 -Cys 6 . We found that human ␤-defensin 3 (hBD3), a recently described member of the growing ␤ family, did not fold preferentially into a native conformation in vitro under various oxidative conditions. Using the orthogonal protection of Cys 1 -Cys 5 and of Cys 1 -Cys 6 , we chemically synthesized six topological analogs of hBD3 with predefined disulfide connectivities, including the (presumably) native ␤ pairing. Unexpectedly, all differently folded hBD3 species exhibited similar antimicrobial activity against Escherichia coli, whereas a wide range of chemotactic activities was observed with these analogs for monocytes and cells transfected by the chemokine receptor CCR6. Furthermore, whereas substitution of all Cys residues by ␣-aminobutyric acid completely abolished the chemotactic activity of hBD3, the bactericidal activity remained unaffected in the absence of any disulfide bridge. Our findings demonstrate that disulfide bonding in hBD3, although required for binding and activation of receptors for chemotaxis, is fully dispensable for its antimicrobial function, thus shedding light on the mechanisms of action for human ␤-defensins and the design of novel peptide antibiotics.

Current Opinion in Immunology, 2005

Trends in Immunology, 2002

Mammalian defensins are small, cationic, antimicrobial peptides encoded by the host that are cons... more Mammalian defensins are small, cationic, antimicrobial peptides encoded by the host that are considered to be important antibiotic-like effectors of innate immunity. By using chemokine receptors on dendritic cells and T cells, defensins might also contribute to the regulation of host adaptive immunity against microbial invasion. Defensins have considerable immunological adjuvant activity and linkage of β β-defensins or selected chemokines to an idiotypic lymphoma antigen has yielded potent antitumor vaccines. The functional overlap between defensins and chemokines is reinforced by reports that some chemokines have antimicrobial activities. Although showing similarity in activity and overall tertiary structure, the evolutionary relationship between defensins and chemokines remains to be determined.

Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucy... more Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucyl-, or threonyl-tRNA synthetase occur in ‫ف‬ 25% of patients with polymyositis or dermatomyositis. We tested the ability of several aminoacyl-tRNA synthetases to induce leukocyte migration. HisRS induced CD4 ϩ and CD8 ϩ lymphocytes, interleukin (IL)-2-activated monocytes, and immature dendritic cells (iDCs) to migrate, but not neutrophils, mature DCs, or unstimulated monocytes. An NH 2 -terminal domain, 1-48 HisRS, was chemotactic for lymphocytes and activated monocytes, whereas a deletion mutant, HisRS-M, was inactive. HisRS selectively activated CC chemokine receptor (CCR)5-transfected HEK-293 cells, inducing migration by interacting with extracellular domain three. Furthermore, monoclonal anti-CCR5 blocked HisRS-induced chemotaxis and conversely, HisRS blocked anti-CCR5 binding. Asparaginyl-tRNA synthetase induced migration of lymphocytes, activated monocytes, iDCs, and CCR3-transfected HEK-293 cells. Seryl-tRNA synthetase induced migration of CCR3-transfected cells but not iDCs. Nonautoantigenic aspartyl-tRNA and lysyl-tRNA synthetases were not chemotactic. Thus, autoantigenic aminoacyl-tRNA synthetases, perhaps liberated from damaged muscle cells, may perpetuate the development of myositis by recruiting mononuclear cells that induce innate and adaptive immune responses. Therefore, the selection of a self-molecule as a target for an autoantibody response may be a consequence of the proinflammatory properties of the molecule itself.

Journal of Leukocyte Biology, 2003

Previous studies have demonstrated that ␤-defensins exhibit chemotactic activity by sharing the c... more Previous studies have demonstrated that ␤-defensins exhibit chemotactic activity by sharing the chemokine receptor CCR6 with the CC chemokine ligand CCL20/macrophage-inflammatory protein-3␣ (MIP-3␣). Structural analysis of CCL20/MIP-3␣ revealed that most of the positively charged residues are concentrated at one area of its topological surface, a characteristic considered to be important for the antimicrobial activity of defensins. Here, we report that similar to defensins, CCL20/MIP-3␣ has antimicrobial effects on Escherichia coli, Pseudomonas aeruginosa, Moraxella catarrhalis, Streptococcus pyogenes, Enterococcus faecium, Staphylococcus aureus, and Candida albicans. Additionally, by screening a total of 30 human chemokines, we have identified an additional 17 human chemokines, which exhibit antimicrobial activity in vitro. Collectively, about two-thirds of the chemokines investigated so far has the capacity to kill microorganisms in vitro, suggesting that antimicrobial activity may be another host-defense function for certain chemokines. Comparison of the structural characteristics between antimicrobial and nonantimicrobial chemokines suggests that topological formation of a large, positively charged electrostatic patch on the surface of the molecule is likely to be a common structural feature of antimicrobial chemokines. J. Leukoc. Biol. 74: 448 -455; 2003.

Defensins, a family of cationic, structurally related, antimicrobial peptides, contribute to host... more Defensins, a family of cationic, structurally related, antimicrobial peptides, contribute to host defense by disrupting the cytoplasmic membrane of microbes. Here we show that human neutrophil defensins selectively induce the migration of human CD4 ؉ /CD45RA ؉ naive and CD8 ؉ , but not CD4 ؉ /CD45RO ؉ memory, T cells. Moreover, human neutrophil defensins are chemotactic for immature human dendritic cells derived from either CD34 ؉ progenitors or peripheral blood monocytes. Upon maturation induced by treatment with tumor necrosis factor ␣ (TNF-␣), dendritic cells lose their responsiveness to human neutrophil defensins. The chemotactic effect of human neutrophil defensins on both T and dendritic cells is pertussis toxin-sensitive, suggesting that a G i␣ protein-coupled receptor is responsible. Human neutrophil defensins are also chemotactic for immature murine dendritic cells. These data suggest that, in addition to their antimicrobial role, human neutrophil defensins also contribute to adaptive immunity by mobilizing T cells and dendritic cells.

Annual Review of Immunology, 2004

Mammals generate a diverse array of antimicrobial proteins, largely represented by defensins or c... more Mammals generate a diverse array of antimicrobial proteins, largely represented by defensins or cathelicidins. The direct in vitro microbicidal activity of antimicrobial proteins has long been considered an important innate immune defense, although the in vivo relevance has only very recently been established for certain defensins and cathelicidins. Mammalian defensins and cathelicidins have also been shown to have multiple receptor-mediated effects on immune cells. Beta-defensins interact with CCR6; murine beta-defensin-2 in addition activates TLR4. Cathelicidins act on FPRL1-expressing cells. Furthermore, several defensins have considerable immunoenhancing activity. Thus, it appears that mammalian antimicrobial proteins contribute to both innate and adaptive antimicrobial immunity.

The impact of health communication is generally enhanced when it is targeted or tailored to the n... more The impact of health communication is generally enhanced when it is targeted or tailored to the needs of a specific population or individual. In a segmentation analysis of the U.S adult population-using data from 2,636 respondents to a mail panel survey-we identified four segments of the adult population that vary significantly with regard to health information preferences based on their degree of engagement in health enhancement, and their degree of independence in health decision making. We also created a brief (10 item), easy-to-administer screening instrument that indicates into which segment people fall. The purpose of this article is to describe the segments, and the screening instrument, and to present initial tests of its validity. We believe this instrument offers a practical tool for differentiating motivationally coherent subgroups of the adult population with regard to their health information preferences, and therefore may have practical value in improving health communication and health services provision efforts. Additional research is needed to further validate the tool and test its utility in guiding the creation of targeted health messages and programs.