Dendritic cell responses to self-assembled monolayers of defined chemistries.
Biomaterial contact triggers dendritic cell (DC) maturation, to an extent depending on the biomaterial, ultimately enhancing an immune response toward associated antigens, implying a role for biomaterials as adjuvants. Self-assembled monolayers (SAM) of alkanethiols on titanium/gold-coated surfaces presenting different chemistries were used to study effects of biomaterial surface chemistry on DC maturation. Although DCs treated with OH, COOH, or NH(2) SAMs showed modest maturation, those treated with CH(3) SAMs were least mature, all based on cytospins, allostimulatory capacity, or maturation marker expression. Surprisingly, DCs treated with CH(3) SAMs secreted highest levels of proinflammatory tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6) but were least mature. Secretion of anti-inflammatory mediators by DCs treated with CH(3) SAMs was not responsible for mitigating DC maturation under these conditions. Interestingly, elevated levels of apoptotic markers were measured associated with DCs and T cells upon CH(3) SAMs contact. Since phagocytosis of apoptotic DCs has strong immunosuppressive effects on DCs, more apoptotic DCs on CH(3) SAMs may account for lower DC maturation. Finally, higher expression of cytotoxic T lymphocyte associated antigen receptor-4 (CTLA-4) on T cells may imply a mechanism of T cell inhibition on CH(3) SAMs.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, USA.
Sucharita P
SP
Shankar
Timothy A
TA
Petrie
Andrés J
AJ
García
Julia E
JE
Babensee
D000276:Adjuvants, Immunologic; D000473:Alkanes / Q000737:chemistry; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000502:physiology; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D060908:CTLA-4 Antigen; D018929:Cell Culture Techniques; D048430:Cell Shape; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D006046:Gold / Q000737:chemistry; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008422:Materials Testing; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013499:Surface Properties; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D014025:Titanium / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000276:Adjuvants, Immunologic; D000473:Alkanes; D015703:Antigens, CD; D001672:Biocompatible Materials; D015415:Biomarkers; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D015850:Interleukin-6; D013438:Sulfhydryl Compounds; D014409:Tumor Necrosis Factor-alpha; D006046:Gold; D014025:Titanium