SERPINB6 (PI6) is a member of the intracellular
serine protease inhibitors (
serpins). Previous studies showed that SERPINB6 is localized mainly in the cytoplasm of endothelial cells, some epithelial cells, monocytes, and neutrophils. In these cells SERPINB6 is thought to prevent cellular damage by scavenging leaking lysosomal
proteases. We show here, using novel, well-defined
monoclonal antibodies, that SERPINB6 is abundantly expressed by mast cells in all organs and by the human mast cell line HMC-1. Gel filtration experiments revealed that the latter cells contain a high-molecular-weight form of SERPINB6, which consists of
sodium dodecyl sulfate (SDS)-stable complexes of this inhibitor with monomeric
beta-tryptase. Expression of SERPINB6 by mast cells was compared with those of
tryptase and CD117 (c-kit) in biopsies from patients with different forms of
mast cell disease. In all cases the lesional mast cells expressed SERPINB6, and, in diffuse
cutaneous mastocytosis and
mastocytoma, SERPINB6 was expressed by a substantially higher number of mast cells when compared with
tryptase. In conclusion, SERPINB6 is abundantly expressed by normal mast cells and by mast cells in
mastocytoma lesions. We suggest that in mast cells, SERPINB6 serves to regulate the activity of endogenous
beta-tryptase in the cytoplasm.