Stage specific gene expression of serpins and their cognate proteases during myeloid differentiation

Abstract

SummaryProteases and their serpin inhibitors are abundantly expressed in haemopoietic and peripheral blood cells. There is, however, relatively little information about the role played by serpins in the control of protease activity within these cells and in the pericellular region. The observation that mutations in the neutrophil elastase gene, which cause cyclic and severe congenital neutropenia, are associated with protease maldistribution gives some clue as to the potential importance of inhibitor proteins. To begin to address the role of protease/inhibitor balance in blood cells we used reverse transcription polymerase chain reaction to examine protease and serpin gene expression in mature peripheral blood cells, differentiating haemopoietic progenitors, leukaemic blasts and haemopoietic cell lines. The results demonstrate stage-specific expression of proteases together with widespread expression of intra-and extra-cellular serpins. The elastase inhibitors monocyte neutrophil elastase inhibitor (MNEI) and antitrypsin (AT) showed overlapping expression. MNEI is predominantly expressed in early haemopoietic progenitors while antitrypsin is mainly expressed in more mature myeloid precursors, peripheral blood granulocytes and mononuclear cells. Our results give an overall picture of serpin and protease gene expression and draws attention to the potential importance of elastase regulators at all stages of myelopoiesis.

Identification of novel stem cell markers using gap analysis of gene expression data

“…In contrast to eukaryotes, prokaryotic serpins are rare and most serpin-containing prokaryotes have only a single serpin gene [ 24 ]. In agreement with our findings, variation in serpin gene expression was recently observed during differentiation in the myeloid lineage [ 25 , 26 ]. Here we give some insight into the functions of the six serpins we identified in our study.…”

SerpinB1 protects the mature neutrophil reserve in the bone marrow

“…Furthermore, during neutrophil bone marrow development, a considerable induction of SERPINB1 expression occurred at the differentiation from myeloblast to promyelocyte, which coincides with the expression of the target granule proteases (NE, CG, and PR-3) [8,9]. Previous reports have indicated that SERPINB1 mRNA was expressed early in neutrophil development [46] and that the SERPINB1 transcription profile was similar to that of primary granule proteins [9]. The absence of defects in serpinB1 Ϫ/Ϫ bone marrow progenitors, which do not contain NSPs, and the correlation between high levels of NSPs and serpinB1 in neutrophils suggest that serpinB1 regulates a proteolytic event important for neutrophil survival.…”

Thrombin and Plasmin Alter the Proteome of Neutrophil Extracellular Traps

“…Nonetheless, we were able to identify all other proteins, even those identified by either Urban et al ( 7 ) or O’Donoghue et al ( 6 ) only, such as histone H1 and catalase, respectively (Table 1 ). Moreover, we were able to identify additional proteins, such as the protease inhibitors SerpinA1 and SerpinB1 which are expressed by neutrophils ( 24 , 25 ) and can inhibit thrombin, ELANE, cathepsin G, and other serine proteases ( 26 , 27 ). Indeed, SerpinB1 has been implicated in NET formation and was also recently identified on NETs ( 20 , 28 ).…”