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  1. Article ; Online: Poly(ethylene glycol)-containing hydrogels modulate α-defensin release from polymorphonuclear leukocytes and monocyte recruitment.

    Lieberthal, Tyler Jacob / Cohen, Hannah Caitlin / Kao, W John

    Journal of biomedical materials research. Part A

    2015  Volume 103, Issue 12, Page(s) 3772–3780

    Abstract: Polymorphonuclear leukocytes (PMNs) release granule proteins as the first line of defense against bacteria and set up chemotactic gradients that result in monocyte infiltration to the site of injury. Although well established, the role of biomaterials in ...

    Abstract Polymorphonuclear leukocytes (PMNs) release granule proteins as the first line of defense against bacteria and set up chemotactic gradients that result in monocyte infiltration to the site of injury. Although well established, the role of biomaterials in regulating adherent PMN degranulation and subsequent PMN-monocyte paracrine interactions is less clear. The aim of this study was to determine how biomaterials affect the degranulation of selected biomarkers and downstream monocyte adhesion and transendothelial migration. Poly(ethylene glycol) (PEG)-containing hydrogels (PEG and an interpenetrating network of PEG and gelatin) promote the release of the α-defensins human neutrophil peptides 1-3, but not azurocidin or monocyte chemotactic protein-1. Although human neutrophil peptides 1-3 are monocyte chemoattractants, no subsequent effects on monocyte transmigration are observed in static conditions. Under flow conditions, monocyte adhesion on human umbilical vein endothelial cells stimulated with tumor necrosis factor-α is elevated in the presence of granule proteins from PMNs adherent on polydimethylsiloxane, but not from PMNs cultured on PEG hydrogels. These results suggest that PEG promotes PMN antimicrobial capacity without enhanced monocyte recruitment.
    MeSH term(s) Biocompatible Materials/metabolism ; Cell Adhesion ; Cell Degranulation ; Cells, Cultured ; Chemotaxis, Leukocyte ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogels/metabolism ; Monocytes/cytology ; Monocytes/metabolism ; Neutrophils/cytology ; Neutrophils/metabolism ; Polyethylene Glycols/metabolism ; alpha-Defensins/metabolism
    Chemical Substances Biocompatible Materials ; Hydrogels ; alpha-Defensins ; Polyethylene Glycols (30IQX730WE)
    Language English
    Publishing date 2015-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2099989-6
    ISSN 1552-4965 ; 1549-3296 ; 0021-9304
    ISSN (online) 1552-4965
    ISSN 1549-3296 ; 0021-9304
    DOI 10.1002/jbm.a.35519
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Poly(ethylene glycol)-containing hydrogels promote the release of primary granules from human blood-derived polymorphonuclear leukocytes.

    Cohen, Hannah Caitlin / Lieberthal, Tyler Jacob / Kao, W John

    Journal of biomedical materials research. Part A

    2014  Volume 102, Issue 12, Page(s) 4252–4261

    Abstract: Polymorphonuclear leukocytes (PMNs) are recruited to sites of injury and biomaterial implants. Once activated, PMNs can exocytose their granule subsets to recruit monocytes (MCs) and mediate MC/macrophage activation. We investigated the release of ... ...

    Abstract Polymorphonuclear leukocytes (PMNs) are recruited to sites of injury and biomaterial implants. Once activated, PMNs can exocytose their granule subsets to recruit monocytes (MCs) and mediate MC/macrophage activation. We investigated the release of myeloperoxidase (MPO), a primary granule marker, and matrix metalloproteinase-9 (MMP-9), a tertiary granule marker, from human blood-derived PMNs cultured on poly(ethylene glycol) (PEG) hydrogels, polydimethylsiloxane (PDMS), tissue culture polystyrene (TCPS) and gelatin-PEG (GP) hydrogels, with and without the presence of the bacterial peptide formyl-Met-Leu-Phe. Supernatants from PMN cultures on PEG-containing hydrogels (i.e., PEG and GP hydrogels) had higher concentrations of MPO than those from PMN cultures on PDMS or TCPS at 2 h. PMNs on all biomaterials released comparable levels of MMP-9 at 2 h, indicating that PMNs cultured on PEG-containing hydrogels have different mechanisms of release for primary and tertiary granules. Src family kinases were involved in the release of MPO from PMNs cultured on PEG hydrogels, TCPS and GP hydrogels and in the release of MMP-9 from PMNs cultured on all four biomaterials. The increased release of primary granules from PMNs on PEG-containing hydrogels did not significantly increase MC chemotaxis, indicating that additional co-effectors in the dynamic inflammatory milieu in vivo modulate PMN-mediated MC recruitment.
    MeSH term(s) Chemotaxis ; Culture Media, Conditioned/chemistry ; Humans ; Hydrogels/chemistry ; Macrophage Activation/drug effects ; Macrophages/cytology ; Macrophages/metabolism ; Matrix Metalloproteinase 9/chemistry ; Monocytes/cytology ; Monocytes/metabolism ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; Neutrophils/cytology ; Neutrophils/metabolism ; Polyethylene Glycols/chemistry ; Secretory Vesicles/chemistry
    Chemical Substances Culture Media, Conditioned ; Hydrogels ; Polyethylene Glycols (3WJQ0SDW1A) ; N-Formylmethionine Leucyl-Phenylalanine (59880-97-6) ; MMP9 protein, human (EC 3.4.24.35) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
    Language English
    Publishing date 2014-02-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2099989-6
    ISSN 1552-4965 ; 1549-3296 ; 0021-9304
    ISSN (online) 1552-4965
    ISSN 1549-3296 ; 0021-9304
    DOI 10.1002/jbm.a.35101
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Biomaterials differentially regulate Src kinases and phosphoinositide 3-kinase-γ in polymorphonuclear leukocyte primary and tertiary granule release

    Cohen, Hannah Caitlin / Frost, Dustin C / Lieberthal, Tyler Jacob / Li, Lingjun / Kao, W. John

    Biomaterials. 2015 May, v. 50

    2015  

    Abstract: In the foreign body response, infiltrating PMNs exocytose granule subsets to influence subsequent downstream inflammatory and wound healing events. In previous studies, we found that PMNs cultured on poly(ethylene glycol) (PEG)-containing hydrogels (i.e., ...

    Abstract In the foreign body response, infiltrating PMNs exocytose granule subsets to influence subsequent downstream inflammatory and wound healing events. In previous studies, we found that PMNs cultured on poly(ethylene glycol) (PEG)-containing hydrogels (i.e., PEG and gelatin + PEG hydrogels) had enhanced primary granule release, yet similar tertiary granule release compared with PMNs cultured on polydimethylsiloxane or tissue culture polystyrene. PMN primary granules contain microbicidal proteins and proteases, which can potentially injure bystander cells, degrade the extracellular matrix, and promote inflammation. Here, we sought to understand the mechanism of the enhanced primary granule release from PMNs on PEG hydrogels. We found that primary granule release from PMNs on PEG hydrogels was adhesion mediated and involved Src family kinases and PI3K-γ. The addition of gelatin to PEG hydrogels did not further enhance PMN primary granule release. Using stable-isotope dimethyl labeling-based shotgun proteomics, we identified many serum proteins – including Ig gamma constant chain region proteins and alpha-1-acid glycoprotein 1 – that were absorbed/adsorbed in higher quantities on PEG hydrogels than on TCPS, and may be involved in mediating PMN primary granule release. Ultimately, this mechanistic knowledge can be used to direct inflammation and wound healing following biomaterial implantation to promote a more favorable healing response.
    Keywords adhesion ; biobased products ; biocompatible materials ; blood proteins ; extracellular matrix ; gelatin ; glycoproteins ; granules ; hydrogels ; inflammation ; phosphotransferases (kinases) ; polydimethylsiloxane ; polyethylene glycol ; polystyrenes ; proteinases ; proteomics ; stable isotopes ; tissue culture
    Language English
    Dates of publication 2015-05
    Size p. 47-55.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 603079-8
    ISSN 0142-9612
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2015.01.050
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Biomaterials differentially regulate Src kinases and phosphoinositide 3-kinase-γ in polymorphonuclear leukocyte primary and tertiary granule release.

    Cohen, Hannah Caitlin / Frost, Dustin C / Lieberthal, Tyler Jacob / Li, Lingjun / Kao, W John

    Biomaterials

    2015  Volume 50, Page(s) 47–55

    Abstract: In the foreign body response, infiltrating PMNs exocytose granule subsets to influence subsequent downstream inflammatory and wound healing events. In previous studies, we found that PMNs cultured on poly(ethylene glycol) (PEG)-containing hydrogels (i.e., ...

    Abstract In the foreign body response, infiltrating PMNs exocytose granule subsets to influence subsequent downstream inflammatory and wound healing events. In previous studies, we found that PMNs cultured on poly(ethylene glycol) (PEG)-containing hydrogels (i.e., PEG and gelatin + PEG hydrogels) had enhanced primary granule release, yet similar tertiary granule release compared with PMNs cultured on polydimethylsiloxane or tissue culture polystyrene. PMN primary granules contain microbicidal proteins and proteases, which can potentially injure bystander cells, degrade the extracellular matrix, and promote inflammation. Here, we sought to understand the mechanism of the enhanced primary granule release from PMNs on PEG hydrogels. We found that primary granule release from PMNs on PEG hydrogels was adhesion mediated and involved Src family kinases and PI3K-γ. The addition of gelatin to PEG hydrogels did not further enhance PMN primary granule release. Using stable-isotope dimethyl labeling-based shotgun proteomics, we identified many serum proteins - including Ig gamma constant chain region proteins and alpha-1-acid glycoprotein 1 - that were absorbed/adsorbed in higher quantities on PEG hydrogels than on TCPS, and may be involved in mediating PMN primary granule release. Ultimately, this mechanistic knowledge can be used to direct inflammation and wound healing following biomaterial implantation to promote a more favorable healing response.
    MeSH term(s) Adsorption ; Adult ; Animals ; Biocompatible Materials/pharmacology ; Blood Proteins/metabolism ; Cattle ; Cell Degranulation/drug effects ; Cells, Cultured ; Cytoplasmic Granules/drug effects ; Cytoplasmic Granules/metabolism ; Humans ; Hydrogels/pharmacology ; Matrix Metalloproteinase 9/metabolism ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; Neutrophils/drug effects ; Neutrophils/enzymology ; Peroxidase/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Polyethylene Glycols/pharmacology ; Polystyrenes/pharmacology ; Receptors, Formyl Peptide/metabolism ; src-Family Kinases/metabolism
    Chemical Substances Biocompatible Materials ; Blood Proteins ; Hydrogels ; Polystyrenes ; Receptors, Formyl Peptide ; Polyethylene Glycols (3WJQ0SDW1A) ; N-Formylmethionine Leucyl-Phenylalanine (59880-97-6) ; Peroxidase (EC 1.11.1.7) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; src-Family Kinases (EC 2.7.10.2) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
    Language English
    Publishing date 2015-02-14
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2015.01.050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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