title: ADAMTS: novel proteases expressed by activated mast cells.
abstract: Here we show that mast cells (MCs) express the metalloproteases of the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, and that ADAMTS expression is influenced by MC activation. Co-culture of MCs with live Gram-positive bacteria caused a profound induction of ADAMTS-9 and -6, as well as down-regulated expression of ADAMTS-5. Similar patterns were also seen after MC activation with calcium ionophore and by immunoglobulin E receptor crosslinking. Moreover, ADAMTS-5, -6 and -9 were all induced by activation of terminally differentiated murine peritoneal MCs and in a human MC line. ADAMTS-9 up-regulation in response to immunoglobulin E receptor crosslinking was strongly dependent on Gö6976-sensitive protein kinase C and partly dependent on nuclear factor of activated T cells and nuclear factor kappa-light-chain-enhancer of activated B cells, respectively. The expression of ADAMTS-5, -6 and -9 was closely linked to MC maturation, as shown by their strong induction during the differentiation of bone marrow precursor cells into mature MCs. ADAMTS family members have been shown to possess aggrecanase activity. Accordingly, MCs were shown to express aggrecanase activity. Finally, ADAMTS-5 protein was detected in MCs by immunocytochemistry. Taken together, the present study reveals ADAMTS expression by MCs and that MC activation regulates the expression of these proteases, thus implicating the ADAMTS family of proteases in MC function.
authors.affiliation: Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry, Uppsala, Sweden. Gianni.Garcia@slu.se
authors.forename: Gianni
authors.initials: G
authors.lastname: García-Faroldi
authors.forename: Elin
authors.initials: E
authors.lastname: Rönnberg
authors.forename: Adolfo
authors.initials: A
authors.lastname: Orro
authors.forename: Gabriela
authors.initials: G
authors.lastname: Calounova
authors.forename: Bengt
authors.initials: B
authors.lastname: Guss
authors.forename: Anders
authors.initials: A
authors.lastname: Lundequist
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D000071116:ADAMTS5 Protein; D000071119:ADAMTS9 Protein; D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D006801:Humans; D008407:Mast Cells / Q000166:cytology* / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018502:Streptococcus equi / Q000254:growth & development / Q000502:physiology
chemical_list: D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D000071119:ADAMTS9 Protein; C412869:ADAMTS9 protein, human; C498489:Adamts5 protein, mouse; C545434:Adamts9 protein, mouse