Modulation of interleukin-2-driven proliferation of human large granular lymphocytes by carbaryl, an anticholinesterase insecticide

Sina Bavari, George P Casale, Roger E. Gold, Edward F. Vitzthum

Research output: Contribution to journalArticle

Abstract

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 α-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 μM, respectively. In contrast, NA had no effect at 0.5 and 5.0 μM, but was inhibitory (16-17%) at 50 μM. 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 reflected 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.

Original languageEnglish (US)
Pages (from-to)61-74
Number of pages14
JournalFundamental and Applied Toxicology
Volume17
Issue number1
DOIs
StatePublished - Aug 27 1991

Fingerprint

Carbaryl
Lymphocytes
Cholinesterase Inhibitors
Insecticides
Interleukin-2
Modulation
Serine Proteases
Thymidine
Blood
Naphthols
Hydrolases
Cell death
Esterases
Metabolites
Protease Inhibitors
Cell culture
Human Activities
Natural Killer Cells
Serine
Culture Media

ASJC Scopus subject areas

  • Toxicology

Cite this

Modulation of interleukin-2-driven proliferation of human large granular lymphocytes by carbaryl, an anticholinesterase insecticide. / Bavari, Sina; Casale, George P; Gold, Roger E.; Vitzthum, Edward F.

In: Fundamental and Applied Toxicology, Vol. 17, No. 1, 27.08.1991, p. 61-74.

Research output: Contribution to journalArticle

@article{ea9341b9aac442649c51de241c27471d,
title = "Modulation of interleukin-2-driven proliferation of human large granular lymphocytes by carbaryl, an anticholinesterase insecticide",
abstract = "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 α-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 μM, respectively. In contrast, NA had no effect at 0.5 and 5.0 μM, but was inhibitory (16-17{\%}) at 50 μM. 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 reflected 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.",
author = "Sina Bavari and Casale, {George P} and Gold, {Roger E.} and Vitzthum, {Edward F.}",
year = "1991",
month = "8",
day = "27",
doi = "10.1016/0272-0590(91)90239-Z",
language = "English (US)",
volume = "17",
pages = "61--74",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Modulation of interleukin-2-driven proliferation of human large granular lymphocytes by carbaryl, an anticholinesterase insecticide

AU - Bavari, Sina

AU - Casale, George P

AU - Gold, Roger E.

AU - Vitzthum, Edward F.

PY - 1991/8/27

Y1 - 1991/8/27

N2 - 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 α-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 μM, respectively. In contrast, NA had no effect at 0.5 and 5.0 μM, but was inhibitory (16-17%) at 50 μM. 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 reflected 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.

AB - 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 α-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 μM, respectively. In contrast, NA had no effect at 0.5 and 5.0 μM, but was inhibitory (16-17%) at 50 μM. 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 reflected 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.

UR - http://www.scopus.com/inward/record.url?scp=0025799470&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025799470&partnerID=8YFLogxK

U2 - 10.1016/0272-0590(91)90239-Z

DO - 10.1016/0272-0590(91)90239-Z

M3 - Article

VL - 17

SP - 61

EP - 74

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 1

ER -