Proteases produced by activated neutrophils are able to release soluble CD23 fragments endowed with proinflammatory effects.
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.
Brignone
C
C
INSERM U343, Hôpital de L'Archet, F-06202 Nice cedex 3, France.
Munoz
O
O
Batoz
M
M
Rouquette-Jazdanian
A
A
Cousin
J L
JL
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
D017455:Receptors, IgE; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534096:Ctsg protein, mouse; D019272:Leukocyte Elastase