Method of inhibiting stenosis and restenosis

Abstract

The invention relates to a method of inhibiting stenosis or restenosis in a subject. In one embodiment, an agent which inhibits recruitment and/or adhesion of neutrophils and mononuclear cells to a site of vascular injury is administered to a subject in need thereof. In another embodiment, a first agent which inhibits recruitment and/or adhesion of neutrophils to a site of vascular injury, and a second agent which inhibits recruitment and/or adhesion of mononuclear cells to a site of vascular injury are administered to a subject in need thereof. In particular embodiments, the agents are antibodies or antigen-binding fragments thereof which bind to CD18 or CCR2.

1 - 48 . (canceled)  
     
     
         49 . A method of inhibiting stenosis in a human blood vessel, the method comprising administering to the human an anti-CD18 antibody which binds specifically with at least the CD18 portion of a mammalian protein which comprises CD18, whereby stenosis is inhibited in the vessel.  
     
     
         50 . The method of  claim 49 , wherein the anti-CD18 antibody has an epitopic specificity which is the same as or similar to that of monoclonal antibody 1B4.  
     
     
         51 . The method of  claim 49 , wherein the protein is a leukocyte cell-surface antigen.  
     
     
         52 . The method of  claim 51 , wherein the antigen is selected from the group consisting of Mac-1, LFA-1, p150,95, and CD11d/CD18.  
     
     
         53 . The method of  claim 51 , wherein binding of the anti-CD18 antibody with the antigen inhibits binding of a natural ligand of the antigen therewith.  
     
     
         54 . The method of  claim 53 , wherein the ligand is selected from the group consisting of ICAM-1, ICAM-2, ICAM-3, C3bi, factor X, fibrin, and fibrinogen.  
     
     
         55 . The method of  claim 49 , wherein binding of the anti-CD18 antibody with the protein modulates at least one function normally associated with binding of a natural ligand of the protein therewith.  
     
     
         56 . The method of  claim 55 , wherein the function is selected from the group consisting of binding of leukocytes with vascular endothelium, translocation of leukocytes through vascular endothelium, infiltration of leukocytes into intimal vascular tissue, release of a chemotactic factor from leukocytes in a vascular tissue, release of a growth factor from leukocytes in a vascular tissue, leukocyte-binding-associated release of a chemotactic factor from a vascular tissue, and leukocyte-binding-associated release of a growth factor from a vascular tissue.  
     
     
         57 . The method of  claim 49 , wherein the blood vessel is a vessel in which the vascular endothelium has been traumatically perturbed.  
     
     
         58 . The method of  claim 49 , wherein the blood vessel is a vessel in which the vascular endothelium has non-traumatically deteriorated.  
     
     
         59 . The method of  claim 49 , wherein the anti-CD18 antibody is an antibody fragment.  
     
     
         60 . The method of  claim 49 , wherein the anti-CD18 antibody is a chimeric antibody.  
     
     
         61 . The method of  claim 49 , wherein the anti-CD18 antibody is a humanized antibody.  
     
     
         62 . The method of  claim 49 , wherein the anti-CD18 antibody is a human antibody.  
     
     
         63 . The method of  claim 49 , wherein the stenosis is restenosis following an angioplastic intervention performed upon the human.  
     
     
         64 . A kit for assessing stenosis in a human blood vessel, the kit comprising an anti-CD18 antibody having a detectable label and an instructional material which describes detecting the anti-CD18 antibody in a blood vessel of the human.  
     
     
         65 . The kit of  claim 64 , wherein the detectable label is a gamma radiation source.  
     
     
         66 . A method of inhibiting interaction of a leukocyte having a CD18-containing cell-surface protein with vascular endothelium in a human, the method comprising contacting the leukocyte with an anti-CD18 antibody, whereby interaction of the leukocyte with vascular endothelium is inhibited.  
     
     
         67 . The method of  claim 66 , wherein the leukocyte is selected from the group consisting of lymphocytes, monocytes, granulocytes, neutrophils, T cells, and basophils.  
     
     
         68 . A method of assessing the presence of leukocytes associated with vascular stenosis in blood obtained from a human, the method comprising 
 contacting the blood with an anti-CD18 antibody and    detecting binding of the anti-CD18 antibody with leukocytes in the blood,    wherein binding of the anti-CD18 antibody with leukocytes in the blood is an indication of the presence of leukocytes associated with vascular stenosis in the blood.    
     
     
         69 . The method of  claim 68 , wherein binding of the anti-CD18 antibody with leukocytes in the blood is quantified.  
     
     
         70 . A method of alleviating a disorder associated with stenosis in a blood vessel of a human, the method comprising administering to the human an anti-CD18 antibody which binds specifically with at least the CD18 portion of a mammalian protein which comprises CD18, whereby stenosis is alleviated in the vessel and the disorder is thereby alleviated.