Human NK cells demonstrate increased adherence and lysis of porcine endothelium following activation with IL-2.

B. Kwiatkowski, J. H. Artrip, Robert E. Michler, S. Itescu

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: For clinical xenotransplantation of pig organs to be successful, the significant barriers of host cellular immunity against the pig will need to be overcome. Natural killer (NK) cells appear to play an important role in rejection of discordant xenografts, and IL-2 activated human NK cells are cytotoxic to human endothelium. We addressed the role of IL-2 activated human and baboon NK cells in the primate immune response to pig xenoantigens in vivo and in vitro. METHODS: Human natural killer (NK) cells were isolated from pooled human peripheral mononuclear cells (PBMC) using density gradient centrifugation method. Phenotype of isolated cells was confirmed by flow cytometry. Purified NK cells were than tasted for spontaneous and IL-2 augmented adhesion and lysis of cultured pig aortic endothelial cells (PAEC) monolayers in a short-term 51 Cr-release assay. The effects of human macrophage derived cytokines TNF alpha and IL-1 on adhesion of IL-2 activated NK cells were studied. RESULTS: Human NK cells demonstrate prominent adherent and lytic activity against pig endothelium, which can be significantly augmented by IL-2. Macrophage derived cytokines can further augment the adherent properties of these NK cells. CONCLUSIONS: These result suggest that human NK cells are likely to play a significant role in rejection of pig-to-human xenografts.

Original languageEnglish (US)
Pages (from-to)21-25
Number of pages5
JournalAnnals of transplantation : quarterly of the Polish Transplantation Society
Volume2
Issue number1
StatePublished - 1997
Externally publishedYes

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Natural Killer Cells
Endothelium
Interleukin-2
Swine
Heterografts
Macrophages
Heterophile Antigens
Cytokines
Heterologous Transplantation
Density Gradient Centrifugation
Papio
Interleukin-1
Cellular Immunity
Primates
Flow Cytometry
Endothelial Cells
Tumor Necrosis Factor-alpha
Phenotype

Cite this

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title = "Human NK cells demonstrate increased adherence and lysis of porcine endothelium following activation with IL-2.",
abstract = "BACKGROUND: For clinical xenotransplantation of pig organs to be successful, the significant barriers of host cellular immunity against the pig will need to be overcome. Natural killer (NK) cells appear to play an important role in rejection of discordant xenografts, and IL-2 activated human NK cells are cytotoxic to human endothelium. We addressed the role of IL-2 activated human and baboon NK cells in the primate immune response to pig xenoantigens in vivo and in vitro. METHODS: Human natural killer (NK) cells were isolated from pooled human peripheral mononuclear cells (PBMC) using density gradient centrifugation method. Phenotype of isolated cells was confirmed by flow cytometry. Purified NK cells were than tasted for spontaneous and IL-2 augmented adhesion and lysis of cultured pig aortic endothelial cells (PAEC) monolayers in a short-term 51 Cr-release assay. The effects of human macrophage derived cytokines TNF alpha and IL-1 on adhesion of IL-2 activated NK cells were studied. RESULTS: Human NK cells demonstrate prominent adherent and lytic activity against pig endothelium, which can be significantly augmented by IL-2. Macrophage derived cytokines can further augment the adherent properties of these NK cells. CONCLUSIONS: These result suggest that human NK cells are likely to play a significant role in rejection of pig-to-human xenografts.",
author = "B. Kwiatkowski and Artrip, {J. H.} and Michler, {Robert E.} and S. Itescu",
year = "1997",
language = "English (US)",
volume = "2",
pages = "21--25",
journal = "Annals of Transplantation",
issn = "1425-9524",
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number = "1",

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TY - JOUR

T1 - Human NK cells demonstrate increased adherence and lysis of porcine endothelium following activation with IL-2.

AU - Kwiatkowski, B.

AU - Artrip, J. H.

AU - Michler, Robert E.

AU - Itescu, S.

PY - 1997

Y1 - 1997

N2 - BACKGROUND: For clinical xenotransplantation of pig organs to be successful, the significant barriers of host cellular immunity against the pig will need to be overcome. Natural killer (NK) cells appear to play an important role in rejection of discordant xenografts, and IL-2 activated human NK cells are cytotoxic to human endothelium. We addressed the role of IL-2 activated human and baboon NK cells in the primate immune response to pig xenoantigens in vivo and in vitro. METHODS: Human natural killer (NK) cells were isolated from pooled human peripheral mononuclear cells (PBMC) using density gradient centrifugation method. Phenotype of isolated cells was confirmed by flow cytometry. Purified NK cells were than tasted for spontaneous and IL-2 augmented adhesion and lysis of cultured pig aortic endothelial cells (PAEC) monolayers in a short-term 51 Cr-release assay. The effects of human macrophage derived cytokines TNF alpha and IL-1 on adhesion of IL-2 activated NK cells were studied. RESULTS: Human NK cells demonstrate prominent adherent and lytic activity against pig endothelium, which can be significantly augmented by IL-2. Macrophage derived cytokines can further augment the adherent properties of these NK cells. CONCLUSIONS: These result suggest that human NK cells are likely to play a significant role in rejection of pig-to-human xenografts.

AB - BACKGROUND: For clinical xenotransplantation of pig organs to be successful, the significant barriers of host cellular immunity against the pig will need to be overcome. Natural killer (NK) cells appear to play an important role in rejection of discordant xenografts, and IL-2 activated human NK cells are cytotoxic to human endothelium. We addressed the role of IL-2 activated human and baboon NK cells in the primate immune response to pig xenoantigens in vivo and in vitro. METHODS: Human natural killer (NK) cells were isolated from pooled human peripheral mononuclear cells (PBMC) using density gradient centrifugation method. Phenotype of isolated cells was confirmed by flow cytometry. Purified NK cells were than tasted for spontaneous and IL-2 augmented adhesion and lysis of cultured pig aortic endothelial cells (PAEC) monolayers in a short-term 51 Cr-release assay. The effects of human macrophage derived cytokines TNF alpha and IL-1 on adhesion of IL-2 activated NK cells were studied. RESULTS: Human NK cells demonstrate prominent adherent and lytic activity against pig endothelium, which can be significantly augmented by IL-2. Macrophage derived cytokines can further augment the adherent properties of these NK cells. CONCLUSIONS: These result suggest that human NK cells are likely to play a significant role in rejection of pig-to-human xenografts.

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