Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Formin protein mDia1 is involved in actin polymerization and plays important roles in the migration and adhesion of hematopoietic cells. The mDia1 encoding gene is located on chromosome 5q, which is commonly deleted in patients with del(5q) myelodysplastic syndromes (MDSs). We previously reported that mice with mDia1 deficiency developed neutropenia that closely mimics MDS. However, the mechanism of neutropenia in these mice and patients with del(5q) MDS remains incompletely defined. Here, we reveal that mDia1 knockout mice show cell-autonomously increased CD11b expression on neutrophils in the peripheral blood and bone marrow. The level of CD11b was also higher in patients with del(5q) MDS compared with normal individuals. Mechanistically, loss of mDia1 significantly attenuated the endocytosis of CD11b on neutrophils, which led to an increased number of neutrophils adhering to the blood vessels in mDia1 knockout mice. Administration of CD11b antibody to mDia1 knockout mice reduced the adhesion of neutrophils to the vessels and rescued neutropenia. Our study reveals the role of mDia1 deficiency in the upregulation of CD11b on neutrophils, which leads to their increased binding to the blood vessels. These results may provide important clues for the pathogenesis of neutropenia in patients with del(5q) MDS.
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PMID:Loss of mDia1 causes neutropenia via attenuated CD11b endocytosis and increased neutrophil adhesion to the endothelium. 2929 12