Document Detail


Modulation of interleukin-2-driven proliferation of human large granular lymphocytes by carbaryl, an anticholinesterase insecticide.
MedLine Citation:
PMID:  1916080     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Studies in other laboratories have provided evidence that the interleukin-2 (IL2) signaling pathway in lymphocytes includes essential, serine proteases. Since the anticholinesterase (antiCHE) insecticides are potent serine hydrolase (esterase and protease) inhibitors, we assessed the ability of carbaryl (CA, a widely used antiCHE insecticide) and alpha-naphthol (NA, a major metabolite of carbaryl) to modulate IL2-driven proliferation of large granular lymphocytes (LGL) purified from human peripheral blood. These cells express nearly all of the natural killer (NK) activity of human peripheral blood. NK cells are normal lymphocytes that respond to IL2 by proliferating and increasing their tumoricidal activity on a per cell basis. Cultures of purified LGL, initiated in the presence of human recombinant IL2, were harvested on culture Day 4, then proliferation was measured as [3H]thymidine incorporation. When added only at the time cultures were initiated. CA inhibited incorporation 10-32%, 35-53%, and 54-57% at 0.5, 5.0, and 50 microM, respectively. In contrast, NA had no effect at 0.5 and 5.0 microM, but was inhibitory (16-17%) at 50 microM. Reexposure to CA or NA, during the incorporation assay, had little effect on the observed inhibition profiles. Chemically induced changes in cell number during an 8-day culture period reflect the chemically induced changes in [3H]thymidine incorporation. Neither CA nor NA produced cell death. Quantitation of both CA and NA by HPLC indicated a rapid loss of CA (ca. 95% in 24 hr) and a much slower loss of NA from the culture medium. CA inhibited human LGL proliferation at concentrations producing little or no inhibition of serum CHE, an indicator of exposure to antiCHE insecticides.
Authors:
S Bavari; G P Casale; R E Gold; E F Vitzthum
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Fundamental and applied toxicology : official journal of the Society of Toxicology     Volume:  17     ISSN:  0272-0590     ISO Abbreviation:  Fundam Appl Toxicol     Publication Date:  1991 Jul 
Date Detail:
Created Date:  1991-11-13     Completed Date:  1991-11-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8200838     Medline TA:  Fundam Appl Toxicol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  61-74     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha 68198-6025.
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MeSH Terms
Descriptor/Qualifier:
Adult
Carbaryl / toxicity*
Cell Adhesion / drug effects
Cell Death / drug effects
Cell Division / physiology*
Humans
Interleukin-2 / physiology*
Killer Cells, Natural / drug effects
Lymphocytes / drug effects*
Male
Naphthols / toxicity
Thymidine / metabolism
Chemical
Reg. No./Substance:
0/Interleukin-2; 0/Naphthols; 50-89-5/Thymidine; 63-25-2/Carbaryl; 90-15-3/1-naphthol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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