title: Stage specific gene expression of serpins and their cognate proteases during myeloid differentiation.
abstract: Proteases 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.
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Burnet Tower, Commercial Road, Prahran, Victoria, Australia.
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Missen
authors.forename: David
authors.initials: D
authors.lastname: Haylock
authors.forename: Genevieve
authors.initials: G
authors.lastname: Whitty
authors.forename: Robert L
authors.initials: RL
authors.lastname: Medcalf
authors.forename: Paul B
authors.initials: PB
authors.lastname: Coughlin
mesh_terms: D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002478:Cells, Cultured; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics*; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics*; D013997:Time Factors; D000515:alpha 1-Antitrypsin / Q000235:genetics
chemical_list: D017396:Plasminogen Activator Inhibitor 2; D015843:Serpins; D000515:alpha 1-Antitrypsin; D010447:Peptide Hydrolases