ヘパリンは,白血球インテグリンMac-1 (CD11b/CD18) とのリガンド結合を阻害する

K Peter¹, M Schwarz, C Conradt

¹Department of Internal Medicine III, University of Heidelberg, Germany. peter@mm31.ukl.uni-freiburg.de

Circulation

|October 6, 1999

まとめ

ヘパリンはインテグリンMac-1と結合し,その機能と白血球の結合を抑制する. この発見は,抗凝固作用を超えて,炎症と細胞増殖に影響を与えるヘパリンの臨床的利点を説明しています.

科学分野:

免疫学免疫学とは
血液学ヘマトロジ
薬理学薬理学とは

背景:

ヘパリンは,抗凝固作用を超えた臨床的利点を示しています.
ヘパリンに対する白血球の粘着は,インテグリンMac-1 (CD11b/CD18) によって媒介されます.
Mac-1の抑制はヘパリンの有益な効果を説明する可能性がある.

研究の目的:

溶性ヘパリンがMac-1機能を調節するかどうかを in vitroおよび in vivoで調査する.
白血球の結合とインテグリン活性におけるヘパリンの役割を調査する.

主な方法:

フローサイトメトリーは,刺激された白血球でヘパリンがMac-1に結合することを実証する.
Mac-1リガンド結合 (フィブリノゲン,X因子,iC3b) の抑制を評価するためのアッセイ.
ICAM-1のモノサイト細胞系とプライマリ白血球を用いた細胞粘着アッセイ.

主要な成果:

不分化ヘパリンは,刺激された単細胞と粒細胞でMac-1に結合する.
ヘパリンは,フィブリノゲン,X因子,iC3bがMac-1に結合することを阻害する.
ヘパリンは,Mac-1抗体阻害に匹敵するICAM-1に対する白血球の粘着を損なう.
低分子量ヘパリンは,また,Mac-1へのフィブリノゲンの結合を阻害する.
In vivoでは,ヘパリンによるフィブリノゲン-Mac-1結合の抑制は,aPTT延長と相関しています.

結論:

ヘパリンは,新しい薬理学的に重要な特性であるMac-1に結合します.
この相互作用は,マック-1リガンド結合を抑制し,凝結と炎症を調節します.
Mac-1に対するヘパリンの効果は,その広範な臨床的利点に寄与する可能性があります.

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