Isolation and characterization of human defensin cDNA clones.
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Discussion
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Implication
Molecular study reveals human defensins are synthesized as precursors in myeloid cells, indicating regulated tissue-specific antimicrobial production.
Key Points
- To isolate and characterize cDNA clones encoding human defensins to determine their protein synthesis mechanisms and patterns of tissue-specific gene expression.
- Screened an HL-60 human promyelocytic leukemia cDNA library to isolate defensin-encoding clones.
- Analyzed sequence characteristics of the defensin precursors and evaluated defensin mRNA expression across normal bone marrow cells, peripheral blood leukocytes, leukemia samples, lung, and intestine tissues.
- Assessed changes in defensin mRNA abundance in HL-60 cell cultures following treatment with dimethyl sulfoxide.
- Sequence analysis of four isolated cDNA clones revealed that defensins are initially synthesized as larger precursor proteins requiring cleavage to generate mature cytotoxic peptides.
- Defensin mRNA expression was present in normal bone marrow cells, peripheral leukocytes from selected leukemia patients, and subsets of lung and intestinal tissues, but was undetectable in normal circulating peripheral blood leukocytes.
- Treatment of HL-60 cells with dimethyl sulfoxide markedly upregulated defensin mRNA transcript levels.
Cite This Study
Daher et al. (1988) studied this question.