CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide-induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation.
The common acute lymphoblastic leukemia antigen (CALLA, CD10), which is expressed on early lymphoid progenitors and neutrophils, is the zinc metalloprotease, neutral endopeptidase 24.11 (NEP, "enkephalinase"). The CD10 cell surface enzyme is known to hydrolyze a variety of biologically active peptides including met-enkephalin, formyl-met-leu-phe (f-MLP), and substance P. These three CD10/NEP substrates induce the migration and aggregation of neutrophils, suggesting that each of the peptides can function as a mediator of neutrophil inflammatory responses. Recently, inhibition of CD10/NEP was found to reduce the concentration of metenkephalin needed to activate human and invertebrate granulocytes by several orders of magnitude. Herein we show that f-MLP and substance P induce rapid changes in neutrophil morphology, migration, and adhesion molecule expression, including upregulation of Mo1 (CD11b/CD18) and shedding of LAM-1 (also known as LECAM-1, Leu8, or TQ-1, the human homologue of murine gp100MEL14). Importantly, these coordinated changes are potentiated by inhibition of cell surface CD10/NEP enzymatic activity. Neutrophil cell surface CD10/NEP enzymatic activity is also shown to be regulated by the activation state of the cell during the time period in which the enzyme has its most pronounced effects. These results suggest that in neutrophils, CD10/NEP functions to control responsiveness to multiple inflammatory peptides.
Shipp
M A
MA
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115.
Stefano
G B
GB
Switzer
S N
SN
Griffin
J D
JD
Reinherz
E L
EL
D000943:Antigens, Differentiation / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D019041:L-Selectin; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D016177:Macrophage-1 Antigen; D019041:L-Selectin; D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015260:Neprilysin