title: Proteases produced by activated neutrophils are able to release soluble CD23 fragments endowed with proinflammatory effects.
abstract: Polymorphonuclear neutrophils (PMNs) are the major source of proteolytic activities involved mainly in tissue injuries observed in chronic inflammatory disorders. High levels of soluble forms of CD23 (the low-affinity receptor for IgE) were found in biological fluids from these patients, and recent reports focused on a CD23-mediated regulation of inflammatory response. In this context, we show here that co-culture of activated PMN with CD23+ B cells resulted in a drastic release of soluble CD23 fragments from the cell surface. This cleavage was inhibited by serine proteases inhibitors, including a1-antitrypsin. We next demonstrated that purified human leukocyte elastase or cathepsin G efficiently cleaved membrane CD23 on B cells with a high specificity. Soluble fragments released by serine proteases-mediated CD23 proteolysis stimulated resting monocytes to produce oxidative burst and proinflammatory cytokine without any co-stimulatory signal. This work strongly supports the idea that the capacity of PMN-derived proteases to release soluble forms of CD23 participates in the inflammatory process mediated by these cells.
authors.affiliation: INSERM U343, Hôpital de L'Archet, F-06202 Nice cedex 3, France.
authors.forename: C
authors.initials: C
authors.lastname: Brignone
authors.forename: O
authors.initials: O
authors.lastname: Munoz
authors.forename: M
authors.initials: M
authors.lastname: Batoz
authors.forename: A
authors.initials: A
authors.lastname: Rouquette-Jazdanian
authors.forename: J L
authors.initials: JL
authors.lastname: Cousin
mesh_terms: D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology*; D017455:Receptors, IgE / Q000378:metabolism*; D012697:Serine Endopeptidases; D012995:Solubility
chemical_list: D017455:Receptors, IgE; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534096:Ctsg protein, mouse; D019272:Leukocyte Elastase