Endothelial CD99 supports arrest of mouse neutrophils in venules and binds to neutrophil PILRs
| Autor: | Masatake Araki, Yu-Tung Li, Kerstin Schäfer, Annette Artz, Kimi Araki, Ken Ichi Yamamura, Ruth Seelige, Ding Jing, Sigrid März, Dietmar Vestweber, Mariana Pacheco-Blanco, Debashree Goswami, Maria Gabriele Bixel |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Endothelium Neutrophils Immunology Intercellular Adhesion Molecule-1 12E7 Antigen Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice Biotin Cell Movement medicine Cell Adhesion Leukocytes Animals Receptors Immunologic Receptor Basement membrane biology Cell Biology Hematology Extravasation Cell biology 030104 developmental biology medicine.anatomical_structure chemistry biology.protein Endothelium Vascular Antibody Blood vessel Protein Binding |
| Zdroj: | Blood. 129(13) |
| ISSN: | 1528-0020 |
| Popis: | CD99 is a crucial regulator of the transmigration (diapedesis) of leukocytes through the blood vessel wall. Here, we report that CD99 acts at 2 different steps in the extravasation process. In agreement with previous antibody-blocking experiments, we found that CD99 gene inactivation caused neutrophil accumulation between venular endothelial cells and the basement membrane in the inflamed cremaster. Unexpectedly, we additionally found that leukocyte attachment to the luminal surface of the venular endothelium was impaired in the absence of CD99. Intravital video microscopy revealed that CD99 supported rapid chemokine-induced leukocyte arrest. Inhibition of leukocyte attachment and extravasation were both solely due to the absence of CD99 on endothelial cells, whereas CD99 on leukocytes was irrelevant. Therefore, we searched for heterophilic ligands of endothelial CD99 on neutrophils. We found that endothelial cells bind to the paired immunoglobulinlike receptors (PILRs) in a strictly CD99-dependent way. In addition, endothelial CD99 was coprecipitated with PILRs from neutrophils that adhered to endothelial cells. Furthermore, soluble CD99 carrying a transferable biotin tag could transfer this tag covalently to PILR when incubated with intact neutrophils. Binding of neutrophils under flow to a surface coated with P-selectin fragment crystallizable (Fc) and intercellular adhesion molecule 1 (ICAM-1) Fc became more shear resistant if CD99 Fc was coimmobilized. This increased shear resistance was lost if neutrophils were preincubated with anti-PILR antibodies. We concluded that endothelial CD99 promotes leukocyte attachment to endothelium in inflamed vessels by a heterophilic ligand. In addition, CD99 binds to PILRs on neutrophils, an interaction that leads to increased shear resistance of the neutrophil attachment to ICAM-1. |
| Databáze: | OpenAIRE |
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