Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells and forms complexes with β-tryptase monomers
- 1 April 2004
- journal article
- Published by American Society of Hematology in Blood
- Vol. 103 (7), 2710-2717
- https://doi.org/10.1182/blood-2003-08-2981
Abstract
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 β-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 β-tryptase in the cytoplasm. (Blood. 2004;103:2710-2717)Keywords
This publication has 35 references indexed in Scilit:
- The Mast Cell in Inflammatory ArthritisThe New England Journal of Medicine, 2003
- Formation of active monomers from tetrameric human beta-tryptaseBiochemical Journal, 2003
- Biochemical and Functional Characterization of Human Transmembrane Tryptase (TMT)/Tryptase γPublished by Elsevier BV ,2002
- Regulation of pro‐apoptotic leucocyte granule serine proteinases by intracellular serpinsImmunology & Cell Biology, 1999
- Proteinase Inhibitor 6 (PI-6) Expression in Human Skin: Induction of PI-6 and a PI-6/Proteinase Complex during Keratinocyte DifferentiationExperimental Cell Research, 1998
- Expression, Purification, and Inhibitory Properties of Human Proteinase Inhibitor 8Biochemistry, 1997
- Proteinase Inhibitor 6 Cannot Be Secreted, Which Suggests It Is a New Type of Cellular SerpinPublished by Elsevier BV ,1996
- Production and characterization of recombinant human proteinase inhibitor 6 expressed in Pichia pastorisBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1995
- Phenotypic Characterization of the Human Mast‐Cell Line HMC‐1Scandinavian Journal of Immunology, 1994
- The ovalbumin family of serpin proteinsFEBS Letters, 1993