RGD Reference Report - CD44-mediated neutrophil apoptosis in the rat. - Rat Genome Database

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CD44-mediated neutrophil apoptosis in the rat.

Authors: Takazoe, K  Tesch, GH  Hill, PA  Hurst, LA  Jun, Z  Lan, HY  Atkins, RC  Nikolic-Paterson, DJ 
Citation: Takazoe K, etal., Kidney Int. 2000 Nov;58(5):1920-30.
RGD ID: 2289387
Pubmed: (View Article at PubMed) PMID:11044212
DOI: Full-text: DOI:10.1111/j.1523-1755.2000.00364.x

BACKGROUND: Apoptosis is an important mechanism by which neutrophils are removed from sites of inflammation, including the kidney. This study investigated whether ligation of the cell-surface adhesion molecule, CD44, can trigger neutrophil apoptosis. METHODS: The anti-rat CD44 antibody OX-50 was used to induce apoptosis of cultured blood neutrophils, as determined by flow cytometry using annexin V staining and by transmission electron microscopy. The functional consequences of OX-50-mediated neutrophil depletion were examined in a rat model of accelerated antiglomerular basement membrane glomerulonephritis. RESULTS: Flow cytometric analysis using the OX-50 antibody, which recognizes the common amino terminal domain of CD44, showed that rat blood neutrophils express very high levels of CD44. The addition of OX-50, but not control antibodies, rapidly induced neutrophil apoptosis in cultured rat blood leukocytes, as demonstrated by annexin V staining and by electron microscopy. Cross-linking of CD44 was essential since F(ab) fragments of the OX-50 antibody failed to induce neutrophil apoptosis. The CD44 ligand hyaluronan and an antibody to the CD44v6 isoform failed to induce neutrophil apoptosis, indicating that OX-50 antibody-mediated neutrophil apoptosis is epitope specific. This effect was specific to neutrophils since the OX-50 antibody did not induce apoptosis in other CD44-expressing cell types (lymphocytes, mesangial cells, or tubular epithelial cells). An injection of OX-50 antibody into normal rats caused a rapid and profound neutropenia, and apoptotic neutrophils could be seen in the blood by electron microscopy. Furthermore, the administration of OX-50 antibody abrogated neutrophil-dependent glomerular injury (proteinuria) on day 1 of rat antiglomerular basement membrane glomerulonephritis, whereas injury on day 10 of the disease (neutrophil independent) was largely unaffected. CONCLUSIONS: The cross-linking of specific epitopes of the CD44 molecule can rapidly induce neutrophil apoptosis in vitro and inhibit neutrophil-dependent renal injury in vivo. This finding suggests that physiological ligands of the CD44 molecule may play an important role in eliminating neutrophils from sites of inflammation, including inflammatory kidney disease.

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Cd44  (CD44 molecule (Indian blood group))

Additional Information