Prodefensin in Plasma of Patients with Chronic Myeloproliferative Disorders. A Parameter of Myelopoietic Activity.

Prodefensins (proHNPs) are the 74 aa antimicrobially inactive precursor peptides of defensins (HNPs). ProHNPs are synthesized in neutrophil precursors from the late promyelocytic stage and until the band cell stage. In promyelocytes, proHNP is proteolytically cleaved to yield 29–30 aa HNPs that are efficiently stored in primary (azurophil) granules. Beyond the promyelocytic stage, proHNPs are no longer proteolytically processed and significant amounts of proHNP escape the cell through constitutive exocytosis. The fate and biological implications of proHNP constitutively secreted from myeloid cells is unclear. We have raised antibodies against a synthetic propiece of proHNP (45 N-terminal amino acids) and developed an accurate, sensitive and specific ELISA for proHNP using these antibodies, with a detection limit of 4.0 ng/ml. We found levels of pro HNP in bone marrow plasma of 9 μg/ml and levels in blood plasma of 1.7 μg/ml. This indicates that the bone marrow is an important organ for generation of this pro-antibiotic molecule giving rise to plasma concentrations in the same order of magnitude as lysozyme and hCAP-18. Studies of plasma from patients with ph- chronic myeloproliferative disorders showed a mean concentration of 3.5 μg/ml indicating that proHNP is a parameter of myelopoietic activity. ProHNP in plasma was apparently not complexed to higher molecular weight structures, yet it was not present in urine. This indicates that proHNP from bone marrow is processed in circulation.