Species specificity of human interleukin-3 demonstrated by cloning and
expression of the homologous rhesus monkey (Macaca mulatta) gene
H Burger, RW van Leen, LC Dorssers, NL Persoon, PJ Lemson and G Wagemaker
Institute of Applied Radiobiology and Immunology TNO, Rijswijk, The
Netherlands.
To enable preclinical studies on homologous interleukin-3 (IL-3) in primate
species, we isolated the gene encoding Rhesus monkey IL-3 (RhIL- 3). The
nucleotide sequence of the RhIL-3 gene displayed 92.9% homology with that
of the human IL-3 (hIL-3) gene. The isolated RhIL-3 gene encodes a
143-amino acid (aa) precursor polypeptide, nine C-terminal residues shorter
than the human protein. Protein homology was found to be 89.5% for the
signal peptide (19 aa) and 80.5% for the mature protein (124 aa).
Comparison of the human and RhIL-3 coding sequences showed that the
majority of substitutions had occurred at amino acid replacement sites
indicating a rapid evolution of the IL-3 protein. After expression of a
genomic fragment in COS cells, RhIL-3 cDNA was constructed, which enabled
large-scale production of the RhIL-3 polypeptide, RhIL-3 produced by
Bacillus licheniformis and purified to homogeneity appeared to be
approximately 100-fold more effective in stimulating Rhesus monkey
hematopoietic progenitors than hIL-3, whereas RhIL-3 and hIL-3 showed
comparable stimulatory activity on normal as well as malignant human
hematopoietic cells. Thus, the rapid evolution of hIL-3 has resulted in a
unidirectional species specificity, which most likely restricts the in vivo
effects of hIL-3 in Macaca species.
Volume 76,
Issue 11,
pp. 2229-2234,
12/01/1990
Copyright © 1990 by The American Society of Hematology
