Linked Life Data

2817813

Source:http://linkedlifedata.com/resource/pubmed/id/2817813

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1989-12-8
pubmed:abstractText
The structure-function relationship of several recombinant human alpha interferons (IFN-alpha) (IFN-alpha 1, IFN-alpha 2, IFN-alpha 4, IFN-alpha 7, IFN-alpha 2/alpha 1 and IFN-delta 4 alpha 1) was investigated with respect to their ability to augment natural killer (NK) cytotoxicity of human peripheral blood mononuclear cells (PBMC) against hemopoietic tumor cell lines. Although all these IFNs significantly augmented NK cytotoxicity against the K562, Daudi and U937 targets, significant quantitave differences were observed in their ability to augment NK. INF-alpha 4, IFN-alpha 2 and IFN-alpha 2/alpha 1 were able to augment NK at low concentrations (less than 0.1 ng/ml), whereas IFN-alpha 7, IFN-alpha 1 and IFN-delta 4 alpha 1 required significantly higher concentrations (3 ng/ml or higher). The cumulative rank order of INFs on the basis of NK augmenting ability was found to be: IFN-alpha 4 approximately IFN-alpha 2 approximately IFN-alpha 2/alpha 1 greater than IFN-alpha 7 greater than IFN-alpha 1 approximately IFN-delta 4 alpha 1. To determine synergism or potentiation in the ability of IFNs to augment NK cytotoxicity, we investigated the effect of simultaneous, sequential and reversed order of treatment of human PBMC by these IFNs. Such potentiation or synergism was not observed. In addition, all these IFNs were able to augment NK cytotoxicity against targets from malignant melanoma cell lines. IFN-alpha 7 augmented regularly and reproducibly NK cytotoxicity in 15 of 19 normal donors examined (79%). This augmentation was blocked by an anti-IFN-alpha antibody. Concentrations of IFN-alpha 7 as low as 0.06 ng/ml were able significantly to augment NK cytotoxicity of PBMC after incubation for one hour at 37 degrees C. In contrast to these findings, IFN-alpha J, an interferon similar to IFN-alpha 7, has been report to be incapable of augmenting NK cytotoxicity and also of interfering with augmentation of NK by other IFNs. Sequential treatment of PBMC first with IFN-alpha 7 and then with other interferons did not prevent the augmentation of NK. Similarly, simultaneous treatment with IFN-alpha 7 and other interferons did not prevent augmentation of NK. In both treatments IFN-alpha J has been reported to prevent augmentation of NK. IFN alpha J and IFN-alpha 7 differ only by one amino acid, at position 107, where a lysine in IFN-alpha J has been replaced by a glutamic acid in the IFN-alpha 7.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0250-7005
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
849-58
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:articleTitle
Regulation of natural killer cytotoxicity by recombinant alpha interferons. Augmentation by IFN-alpha 7, an interferon similar to IFN-alpha J.
pubmed:affiliation
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't