Function associated molecules on nonspecific cytotoxic cells: Role in calcium signaling, redirected lysis, and modulation of cytotoxicity

Donald L. Evans, David T. Harris, Liliana Jaso-Friedmann

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Monoclonal antibodies (mAbs) specific for a putative antigen receptor (function associated molecule, FAM) on fish NCC were tested for their ability to initiate signal transduction responses. Anti-FAM hybridoma target cells were significantly lysed by NCC when tested by redirected lysis (RL). Redirected lysis was enhanced by 1-h pretreatment of the NCC with anti-FAM mAb; however, 18-h pretreatment produced significant inhibition. The effects of the calcium ionophore A23187 on RL were also examined: 10-4 M but not 10-5 M A23187 significantly increased RL. Purified NCC were treated with mAb and cellular DNA synthesis was determined. Significant increases in NCC incorporation of tritiated thymidine were measured 72 h after treatment with mAb. Experiments were also conducted to determine levels of free cytosolic calcium in NCC following mAb binding. Anti-FAM mAb binding produced a rapid rise in cytosolic calcium (200-500 nM) determined by Fura-2/AM fluorescence. Calcium ionophore A23187, PHA, and Con-A treatment of NCC also produced significantly increased [Ca2+]i. Target cell binding by NCC caused a three-fold increase in [Ca2+]i. These data suggest that triggering of the FAM may initiate a signal(s) that activates cytotoxicity, increases cytosolic free calcium concentrations, and initiates DNA synthesis.

Original languageEnglish (US)
Pages (from-to)383-394
Number of pages12
JournalDevelopmental and Comparative Immunology
Volume16
Issue number5
DOIs
Publication statusPublished - 1992

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Keywords

  • A23187
  • Monoclonal antibodies
  • Nonspecific cytotoxic cells
  • Redirected lysis
  • Signal transduction

ASJC Scopus subject areas

  • Developmental Biology
  • Immunology

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