Comparison of the cytotoxic effects of receptor tyrosine kinase inhibitors on macrophage functions; possible side effects in the immune defense

A. Hrabák, Gyöngyi Bökönyi, L. Őrfi, Tamás Bajor, G. Kéri

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Certain receptor tyrosine kinase (RTK) inhibitors reduced the phagocytic capacity of rat macrophages, without influencing the binding of bacteria to macrophage surface. The NO production of elicited rat macrophages was also decreased due to the inhibition of the expression of NOS II. The most potent inhibitory compound was PD166326 (6-(2,6-dichloro-phenyl)-2-(4-hydroxy-phenylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one) belonging to a family of RTK inhibitors of broad spectra. These impairing effects could be explained by the apoptosis inducing property of the inhibitor, evidenced by the destroyed mitochondrial membrane potential. The MTT cell viability test indicated a slight, but significant injury of macrophages. In addition to this compound, two other tested RTK inhibitors caused less marked impairment of macrophage functions, while four compounds were not efficient on macrophages at all. Nevertheless, these damaging effects of the inhibitors did not reduce the anti-tumor effect of the RTK inhibitors on COS 7 cells as evidenced by MTT test and apoptosis study. However, these side effects may be important when RTK inhibitors are selected against tumor growth, indicating that certain inhibitors may impair the immune defense during therapeutical application.

Original languageEnglish
Pages (from-to)169-175
Number of pages7
JournalImmunology Letters
Volume107
Issue number2
DOIs
Publication statusPublished - Nov 15 2006

Fingerprint

Receptor Protein-Tyrosine Kinases
Macrophages
Apoptosis
Mitochondrial Membrane Potential
COS Cells
Nitric Oxide Synthase Type II
Neoplasms
Cell Survival
Bacteria
Wounds and Injuries
Growth

Keywords

  • Apoptosis
  • Macrophages
  • Nitric oxide synthesis
  • Phagocytosis
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Comparison of the cytotoxic effects of receptor tyrosine kinase inhibitors on macrophage functions; possible side effects in the immune defense. / Hrabák, A.; Bökönyi, Gyöngyi; Őrfi, L.; Bajor, Tamás; Kéri, G.

In: Immunology Letters, Vol. 107, No. 2, 15.11.2006, p. 169-175.

Research output: Contribution to journalArticle

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