Development of a lymphocyte-transformation-assay for peripheral blood lymphocytes of the harbor porpoise and detection of cytokines using the reverse-transcription polymerase chain reaction

Vet Immunol Immunopathol. 2004 Mar;98(1-2):59-68. doi: 10.1016/j.vetimm.2003.10.002.

Abstract

Impairment of immune function is suggested to play a contributing role for the increasing incidence of infectious diseases in the harbor porpoise (Phocoena phocoena) of the North and Baltic Seas. Both, lymphocyte-transformation-assay of peripheral blood lymphocytes (PBMC) and detection of cytokine expression are important tools for the characterization of the cellular immune response. To evaluate optimal parameters for the lymphocyte-transformation-assay isolated blood lymphocytes from four healthy harbor porpoises were stimulated with different concentrations of concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Cell proliferation was measured photometrically after 72 h using 5-bromo-deoxyuridine-assay and stimulation indices were calculated. The expression of pro- and anti-inflammatory cytokines such as interleukin (IL)-2, IL-4, IL-6, IL-10, transforming growth factor (TGF)-beta, and tumor necrosis factor (TNF)-alpha was investigated in control and mitogen-stimulated lymphocytes using reverse-transcription polymerase chain reaction (RT-PCR). Primers for IL-2, IL-4 and IL-6 were selected from published cDNA-sequences of other cetaceans. Established canine and human primers were taken for the detection of TNF-alpha, TGF-beta, IL-10 and the house keeping transcript glyceraldehyde-3-phosphate dehydrogenase (GAPDH), respectively. Specificity of the amplicon was confirmed by DNA sequence analysis and comparison with nucleotide sequences of other marine and terrestrial mammals. Con A and PHA represented the most powerful mitogens for harbor porpoise lymphoid cells at concentrations of 5 and 2 microg/ml, respectively, while PWM induced a comparatively low maximum proliferation at a concentration of 2 microg/ml. GAPDH was amplified in non-stimulated and all mitogen-stimulated cells. With the exception of IL-10 none of the other cytokines were detected in non-stimulated cells. Transcription of IL-4, IL-6, IL-10, TNF-alpha and TGF-beta-mRNA was observed after incubation with all the three phytomitogens, whereas IL-2 was only detected in Con A and PWM treated cells. Lymphocyte-transformation-assay and RT-PCR for detection of cytokines will allow to investigate possible impaired immune function in the harbor porpoise in future studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Concanavalin A / pharmacology
  • Cytokines / genetics*
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • In Vitro Techniques
  • Interleukins / genetics
  • Lymphocyte Activation*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Molecular Sequence Data
  • Phytohemagglutinins / pharmacology
  • Pokeweed Mitogens / pharmacology
  • Porpoises / genetics*
  • Porpoises / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / genetics
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cytokines
  • DNA Primers
  • DNA, Complementary
  • Interleukins
  • Phytohemagglutinins
  • Pokeweed Mitogens
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Concanavalin A

Associated data

  • GENBANK/AF346294
  • GENBANK/AF346295
  • GENBANK/AF346296
  • GENBANK/AF346297
  • GENBANK/AF346298
  • GENBANK/AF346299
  • GENBANK/AF346300