Enolase-1 promotes plasminogen-mediated recruitment of monocytes to the acutely inflamed lung.
Cell surface-associated proteolysis plays a crucial role in the migration of mononuclear phagocytes to sites of inflammation. The glycolytic enzyme enolase-1 (ENO-1) binds plasminogen at the cell surface, enhancing local plasmin production. This study addressed the role played by ENO-1 in lipopolysaccharide (LPS)-driven chemokine-directed monocyte migration and matrix invasion in vitro, as well as recruitment of monocytes to the alveolar compartment in vivo. LPS rapidly up-regulated ENO-1 cell-surface expression on human blood monocytes and U937 cells due to protein translocation from cytosolic pools, which increased plasmin generation, enhanced monocyte migration through epithelial monolayers, and promoted matrix degradation. These effects were abrogated by antibodies directed against the plasminogen binding site of ENO-1. Overexpression of ENO-1 in U937 cells increased their migratory and matrix-penetrating capacity, which was suppressed by overexpression of a truncated ENO-1 variant lacking the plasminogen binding site (ENO-1DeltaPLG). In vivo, intratracheal LPS application in mice promoted alveolar recruitment of monocytic cells that overexpressed ENO-1, but not of cells overexpressing ENO-1DeltaPLG. Consistent with these data, pneumonia-patients exhibited increased ENO-1 cell-surface expression on blood monocytes and intense ENO-1 staining of mononuclear cells in the alveolar space. These data suggest an important mechanism of inflammatory cell invasion mediated by increased cell-surface expression of ENO-1.
Wygrecka
Malgorzata
M
Department of Biochemistry, Faculty of Medicine, University of Giessen Lung Center, Giessen, Germany.
Marsh
Leigh M
LM
Morty
Rory E
RE
Henneke
Ingrid
I
Guenther
Andreas
A
Lohmeyer
Juergen
J
Markart
Philipp
P
Preissner
Klaus T
KT
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000954:Antigens, Surface / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010958:Plasminogen / Q000378:metabolism / Q000494:pharmacology*; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020298:U937 Cells
D000906:Antibodies; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D025521:Tumor Suppressor Proteins; D010958:Plasminogen; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase