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

TitleBiomaterials differentially regulate Src kinases and phosphoinositide 3-kinase-γ in polymorphonuclear leukocyte primary and tertiary granule release
Authors
KeywordsAcute inflammation
Poly(ethylene glycol)
Neutrophil
Gelatin
Degranulation
Protein adsorption
Issue Date2015
Citation
Biomaterials, 2015, v. 50, n. 1, p. 47-55 How to Cite?
Abstract© 2015 Elsevier Ltd. 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.
Persistent Identifierhttp://hdl.handle.net/10722/216129
ISSN
2015 Impact Factor: 8.387
2015 SCImago Journal Rankings: 3.565

 

DC FieldValueLanguage
dc.contributor.authorCohen, Hannah Caitlin-
dc.contributor.authorFrost, Dustin C.-
dc.contributor.authorLieberthal, Tyler Jacob-
dc.contributor.authorLi, Lingjun-
dc.contributor.authorKao, W. John-
dc.date.accessioned2015-08-25T10:21:02Z-
dc.date.available2015-08-25T10:21:02Z-
dc.date.issued2015-
dc.identifier.citationBiomaterials, 2015, v. 50, n. 1, p. 47-55-
dc.identifier.issn0142-9612-
dc.identifier.urihttp://hdl.handle.net/10722/216129-
dc.description.abstract© 2015 Elsevier Ltd. 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.-
dc.languageeng-
dc.relation.ispartofBiomaterials-
dc.subjectAcute inflammation-
dc.subjectPoly(ethylene glycol)-
dc.subjectNeutrophil-
dc.subjectGelatin-
dc.subjectDegranulation-
dc.subjectProtein adsorption-
dc.titleBiomaterials differentially regulate Src kinases and phosphoinositide 3-kinase-γ in polymorphonuclear leukocyte primary and tertiary granule release-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.biomaterials.2015.01.050-
dc.identifier.scopuseid_2-s2.0-84932623160-
dc.identifier.volume50-
dc.identifier.issue1-
dc.identifier.spage47-
dc.identifier.epage55-
dc.identifier.eissn1878-5905-

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