Cloning and expression of the cDNA encoding mouse neutrophil gelatinase: demonstration of coordinate secondary granule protein gene expression during terminal neutrophil maturation.

The 92-kD form of human type IV collagenase (gelatinase) is a member of the matrix metalloproteinase family. It is restricted in its expression to the granulocytic lineage of white blood cells. Within neutrophils it resides in secondary granules, which are markers of terminal myeloid differentiation. We have isolated and sequenced the cDNA encoding the murine counterpart to the human 92-kD metalloproteinase from a macrophage cDNA library. The human and murine genes are highly homologous and exist in an identical form in neutrophils and monocyte-macrophages in both species. Two polyadenylation signals are present in the murine 3' untranslated sequence, accounting for equal expression of two messenger RNAs. We have shown that expression of gelatinase mRNA is controlled in a coordinate fashion together with lactoferrin, also a component of neutrophil secondary granules, and that this control occurs at the level of transcription. This is the first definitive demonstration of coordinate transcriptional regulation of secondary granule protein gene expression, a feature of normal myelopoiesis that is deranged in leukemogenesis.