patient with Chediak-Higashi syndrome

Accepted for publication 8 November 1994 Abstract Aims-To determine whether neutrophil elastase and cathepsin G are expressed, at transcriptional or translational levels, in the bone marrow from a patient with Chediak-Higashi syndrome. Methods-Blood neutrophils were isolated from three patients with Chediak-Higashi disease and bone marrow was collected from one. Cell lysates were analysed for neutrophil elastase and cathepsin G activity by enzyme linked immunosorbent assay and western immunoblotting. Northern blotting was used to detect messenger RNA (mRNA) for cathepsin G, elastase and ,-actin in bone marrow extracts, and immunohistochemistry was used to localise the enzymes in marrow myeloid cells. Results-Elastase and cathepsin G were not detected in blood neutrophils from the patients with Chediak-Higashi disease, but were present in bone marrow cells, although immunohistochemistry showed they were not within cytoplasmic granules. The concentrations of elastase and cathepsin G in Chediak-Higashi bone marrow were about 25 and 15%, respectively, of those in normal marrow. Quantitative scanning of northern blots showed that elastase and cathepsin GmRNA, corrected for ,-actin mRNA, were expressed equally in normal marrow. Conclusions-Transcription of elastase and cathepsin G mRNA in promyelocytes of patients with Chediak-Higashi disease is normal, but the protein products are deficient in these cells and absent in mature neutrophils. This suggests that the translated proteins are not packaged into azurophil granules but are degaded or secreted from the cells. ( Clin Pathol: Mol Pathol 1995;48:M28-M34)