Linked Life Data

3257170

Source:http://linkedlifedata.com/resource/pubmed/id/3257170

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1988-2-23
pubmed:abstractText
We have examined the effects of protein kinase C (PK-C) stimulation and cytosolic Ca2+ elevation on the in vitro induction of non-histocompatibility-restricted tumoricidal activity from human peripheral blood lymphocytes. The tumor cytolytic activity, as well as the number of cells recovered from interleukin 2 (IL-2)-stimulated cultures, was enhanced by the addition of the PK-C stimulator, phorbol dibutyrate (PDBu), but not non-PK-C-activating phorbol ester analogues while the Ca2+ ionophore, ionomycin, did not significantly alter development of IL-2-induced tumor cytolytic activity nor enhance cell yield. Neither PDBu nor ionomycin, alone or in combination, induced tumoricidal activity. The addition of both PDBu and ionomycin to recombinant interleukin 2 (rIL-2)-exposed cultures produced a strong mitogenic response and high cell yield, although Daudi cell killing measured at Day 5 was completely abolished. This abrogation of lymphokine-activated killer cell activity was seen as early as 24 h following exposure to PDBu and ionomycin, reaching 50% following 2 days of exposure. When lymphocytes mitogenically expanded by primary exposure to PDBu and ionomycin and then washed free of these agents were further cultured with rIL-2 alone, proliferation continued, and substantial cytolytic activity for Daudi cells was induced. The development of this postexpansion cytotoxic activity was not dependent on the addition of exogenous rIL-2 during the primary cultures. Fractionation of cells into large granular lymphocytes and small T-lymphocytes indicated that only the large granular lymphocytes proliferate in response to rIL-2 alone. Both large granular lymphocytes and small T-lymphocytes proliferate in response to the addition of PDBu and ionomycin, and both populations of cells developed tumor cytolytic activity following removal of PDBu and ionomycin and subsequent culture in rIL-2. These data suggest that PK-C and Ca2+ signals play key roles in the regulation and/or proliferation of tumor cytotoxic lymphocytes or their precursors and that manipulation of those signals can be utilized to produce substantially more tumoricidal activity from lymphocyte populations than can be achieved with rIL-2 alone.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
635-40
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Alteration of human lymphokine-activated killer cell activity by manipulation of protein kinase C and cytosolic Ca2+.
pubmed:affiliation
Department of Pharmacology and Toxicology, Medical College of Virginia Commonwealth University, Richmond 23298.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.