Leukocyte Histidine Decarboxylase: Properties and Activity in Myeloproliferative Disorders

1. Histidine decarboxylase was assayed in extracts from human leukocytes and the properties of the enzyme studied.

2. Leukocyte histidine decarboxylase was found to be substrate-specific, to require pyridoxal phosphate as co-enzyme, and to be inhibited by alpha-hydrazino analog of histidine (MK 785), a selective inhibitor of the specific histidine decarboxylase occuring in rat tissue. A non-specific L-aromatic amino acid decarboxylase was also demonstrated in leukocyte extracts, which possessed little activity toward histidine.

3. Cellular localization studies revealed that mature neutrophils and basophils possessed most of the histidine decarboxylase activity exhibited by mixed leukocyte preparations. Mature eosinophils, small lymphocytes, and immature myeloid cells (myeloblasts and promyelocytes) showed little histidine decarboxylase activity.

4. In the clinical studies, patients with uncontrolled polycythemia vera, "spent" polycythemia, myelofibrosis with myeloid metaplasia, and chronic myelocytic leukemia, showed increased leukocyte enzyme activity when compared to a control group composed of normal subjects and patients with relative polycythemia. This increased activity appears to represent a true increase in enzyme activity per granulocyte, and is believed to account for the elevated leukocyte histamine content demonstrated in patients with myeloproliferative disorders.