- 作者: Yu-Lun Tseng; Hui-Chin Peng; Tur-Fu Huang
- 作者服務機構: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: Disintegrins are a group of Arg (or Lys)-Gly-Asp-contain-ing snake venom proteins which inhibit platelet aggrega-tion via the blockade of αllbβN3 integrin.Here, we studiedthe effect of rhodostomin, a disintegrin purified from thevenom of Calloselasma rhodostoma, on the functions ofneutrophils. By flow cytometric analysis of whole blood,we found that rhodostomin interacted with leukocytes ofthe myeloid and monocytic lineage as well as with plate-lets. The binding of rhodostomin to neutrophils couldreach saturation in a dose-dependent manner, and itsbinding was increased in neutrophils stimulated withphorbol 12-myristate 13-acetate(PMA) and N-formyl-Met-Leu-Phe.EDTA did not inhibit the binding of rhodo-stomin. In addition,bound rhodostomin was not inter-nalized. Soluble fibrinogen,a natural ligand of Mac-1(CD11b/CD18, αMβ2),and the peptide, GRGDS, inhibitedthe binding of rhodostomin to PMA-activated neutro-phils, while 7E3, a monoclonal antibody(mAb) raisedagainst β3 integrin,or mAbs raised against αm and β2integrin did not. Rhodostomin blocked the Mac-1-depen-dent adhesion of neutrophils to immobilized fibrinogen,in parallel with decreasing the production of superoxidefrom adherent neutrophils. Taken together, our resultsindicate that rhodostomin binds to activated neutrophilsin an RGD-dependent manner, blocks the adhesion ofactivated neutrophils to fibrinogen and attenuates super-oxide production, suggesting that rhodostomin mayhave anti-inflammatory properties.
- 中文關鍵字: --
- 英文關鍵字: --