Temporary serine protease inhibition and the role of SPINK2 in human bone marrow
Vincenza Barresi,
Virginia Di Bella,
Luca Lo Nigro,
Anna Provvidenza Privitera,
Paola Bonaccorso,
Chiara Scuderi,
Daniele Filippo Condorelli
Affiliations
Vincenza Barresi
Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy; Corresponding author
Virginia Di Bella
Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy
Luca Lo Nigro
Cytogenetic-Cytofluorimetric-Molecular Biology Lab, 95123 Catania, Italy; Center of Pediatric Hematology-Oncology, Azienda Policlinico – San Marco, 95123 Catania, Italy
Anna Provvidenza Privitera
Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy
Paola Bonaccorso
Cytogenetic-Cytofluorimetric-Molecular Biology Lab, 95123 Catania, Italy; Center of Pediatric Hematology-Oncology, Azienda Policlinico – San Marco, 95123 Catania, Italy
Chiara Scuderi
Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy
Daniele Filippo Condorelli
Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy; Corresponding author
Summary: Protease temporary inhibitors are true substrates that bind the catalytic site with high affinity but are slowly degraded, thus acting as inhibitor for a defined time window. Serine peptidase inhibitor Kazal type (SPINK) family is endowed with such functional property whose physiological meaning is poorly explored. High expression of SPINK2 in some hematopoietic malignancies prompted us to investigate its role in adult human bone marrow. We report here the physiological expression of SPINK2 in hematopoietic stem and progenitor cells (HSPCs) and mobilized cluster differentiation 34 (CD34)+ cells. We determined the SPINK2 degradation constant and derived a mathematical relationship predicting the zone of inhibited target protease activity surrounding the SPINK2-secreting HSPCs. Analysis of putative target proteases for SPINK2 revealed the expression of PRSS2 and PRSS57 in HSPCs. Our combined results suggest that SPINK2 and its target serine proteases might play a role in the intercellular communication within the hematopoietic stem cell niche.
