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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wang, Yue Wu, Jianming Newton, Robert Walcheck, Bruce Bahaie, Nooshin S. Long, Chunmei |
| Description | Author Affiliation: Wang Y ( Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA.) |
| Abstract | CD16b (FcγRIIIb) is exclusively expressed by human neutrophils and binds IgG in immune complexes. Cell surface CD16b undergoes efficient ectodomain shedding upon neutrophil activation and apoptosis. Indeed, soluble CD16b is present at high levels in the plasma of healthy individuals, which appears to be maintained by the daily turnover of apoptotic neutrophils. At this time, the principal protease responsible for CD16b shedding is not known. We show that CD16b plasma levels were significantly decreased in patients administered a selective inhibitor targeting the metalloproteases ADAM10 and ADAM17. Additional analysis with inhibitors selective for ADAM10 or ADAM17 revealed that only inhibition of ADAM17 significantly blocked the cleavage of CD16b following neutrophil activation and apoptosis. CD16b shedding by ADAM17 was further demonstrated using a unique ADAM17 function-blocking mAb and a cell-based ADAM17 reconstitution assay. Unlike human CD16, however, mouse CD16 did not undergo efficient ectodomain shedding upon neutrophil stimulation or apoptosis, indicating that this mechanism cannot be modeled in normal mice. Taken together, our findings are the first to directly demonstrate that ADAM17 cleaves CD16 in human leukocytes. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 3 |
| Volume Number | 1833 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-03-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | ADAM Proteins Physiology Apoptosis Neutrophils Metabolism Protease Inhibitors Pharmacology Receptors, IgG Antagonists & Inhibitors Amino Acid Sequence Animals Blotting, Western Fibroblasts Cytology Drug Effects Flow Cytometry GPI-Linked Proteins Mice Mice, Knockout Molecular Sequence Data Neutrophil Activation Pathology Sequence Homology, Amino Acid Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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