EXPRESSION OF A SOLUBLE AND FUNCTIONAL FORM OF THE HUMAN BETA-2 INTEGRIN CD11B/CD18

被引:72
作者
DANA, N
FATHALLAH, DM
ARNAOUT, MA
机构
[1] MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114
[2] HARVARD UNIV,SCH MED,BOSTON,MA 02115
关键词
RECOMBINANT BETA-2 INTEGRINS; COMPLEMENT RECEPTORS; LEUKOCYTE-ENDOTHELIAL ADHESION; INFLAMMATORY REACTIONS; REPERFUSION INJURY;
D O I
10.1073/pnas.88.8.3106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Polymorphonuclear cells and monocytes (phagocytes) are a critical component of host defense against infections. However, these cells also play a significant role in host tissue damage in many noninfectious diseases, such as ischemia-reperfusion injury syndromes and rejection of transplanted organs. The leukocyte adhesion molecule family CD11/CD18 (beta-2 integrins) is critical to the function of polymorphonuclear cells and monocytes in inflammation and injury. Inherited deficiency of CD11/CD18 impairs phagocyte chemotaxis, adhesion and transmigration across endothelium, and clearance of invading microorganisms through phagocytosis and cell-mediated killing. Furthermore, murine monoclonal antibodies directed against the CD11b/CD18 (CR3) heterodimer have been shown to reduce, by 50%-80%, phagocyte-mediated ischemia-reperfusion injury in several organ systems, such as the myocardium, liver, and gastrointestinal tract and to inhibit development of insulin-dependent diabetes mellitus in nonobese diabetic (NOD) mice. Expression of CD11b/CD18 in a soluble and functional form might therefore be potentially useful as an anti-inflammatory agent. We have now expressed a recombinant soluble heterodimeric form of this human beta-2 integrin, normally expressed as two noncovalently associated membrane-bound subunits. The secreted receptor exhibited direct and specific binding to its ligand, iC3b, the major complement C3 opsonin, and inhibited binding of polymorphonuclear cells to recombinant interleukin 1-activated endothelium.
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页码:3106 / 3110
页数:5
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