Induction of non-specific suppressor cells in normal lewis rats by a novel azaspirane SK&F 105685

Alison M. Badger, Andrew G. King, James E. Talmadge, David A. Schwartz, Donald H. Picker, Christopher K. Mirabelli, Nabil Hanna

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

SK&F 105685 (N,N-Dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine dihydrochloride) is a novel azaspirane which has therapeutic activity in rat models of autoimmune disease. In this study, we have demonstrated that SK&F 105685 is a potent inducer of non-specific suppressor cells (SC). Oral administration of 15-30 mg/kg/day results in the generation of SC in the spleen, lymph nodes and bone marrow, but not the thymus of Lewis rats. Splenic SC suppress Con-A-induced proliferation in co-culture assays at effector-responder ratios of 1:1 to 1:64. SC are radiation resistant (2000 R), non-T, non-B cells, partially adherent to plastic surfaces and are enriched in a 1.07 g/ml fraction of a Percoll density gradient. Their activity is increased, rather than ablated, by indomethacin. No definitive changes in Ig+, OX-19+, OX-8+, W3/25+ or asialo GM1+ cells could be detected in the spleens of treated rats compared to control untreated animals. Elevated levels of both radiation-sensitive and radiation-resistant suppressor cells were found in the bone marrow of treated rats in addition to the radiosensitive SC normally present in this tissue.

Original languageEnglish (US)
Pages (from-to)485-500
Number of pages16
JournalJournal of Autoimmunity
Volume3
Issue number4
DOIs
StatePublished - Aug 1990

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Radiation
Spleen
Bone Marrow
azaspirane
Coculture Techniques
Indomethacin
Thymus Gland
Autoimmune Diseases
Plastics
Oral Administration
Lymph Nodes
Therapeutics
SK&F 105685
Percoll
asialo GM1 ganglioside

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Induction of non-specific suppressor cells in normal lewis rats by a novel azaspirane SK&F 105685. / Badger, Alison M.; King, Andrew G.; Talmadge, James E.; Schwartz, David A.; Picker, Donald H.; Mirabelli, Christopher K.; Hanna, Nabil.

In: Journal of Autoimmunity, Vol. 3, No. 4, 08.1990, p. 485-500.

Research output: Contribution to journalArticle

Badger, Alison M. ; King, Andrew G. ; Talmadge, James E. ; Schwartz, David A. ; Picker, Donald H. ; Mirabelli, Christopher K. ; Hanna, Nabil. / Induction of non-specific suppressor cells in normal lewis rats by a novel azaspirane SK&F 105685. In: Journal of Autoimmunity. 1990 ; Vol. 3, No. 4. pp. 485-500.
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