Method of inhibiting the emigration of cells from the intravascular compartment into tissues

Abstract

A method of inhibiting the emigration of cells from the intravascular compartment into tissues (or through any membrane limiting any body compartment from another) by confronting the cells with an agonist specific for receptors involved with migration of said cells via a receptor thereby making the cell unresponsive to further activation.

1 . A method of inhibiting the emigration of cells from the intravascular compartment into tissues (or through any membrane limiting any body compartment from another) by confronting the cells with an agonist specific for receptors involved with migration of said cells via a receptor thereby making the cell unresponsive to further activation.  
     
     
         2 . A method according to  claim 1 , wherein the cells are blood circulating cells and the intravascular compartiment is the blood stream.  
     
     
         3 . The method of  claim 1  wherein the cells are leukocytes.  
     
     
         4 . The method of  claim 1  wherein the cell is unresponsive to further activation for emigration to tissues after confrontation with an agonist.  
     
     
         5 . The method according to  claim 1  wherein the agonist used to inhibit the migration of the cells is a chemoattractant binding to a corresponding receptor or molecule binding to such a receptor.  
     
     
         6 . The method of  claim 5  wherein the chemo-attractant is selected from the group consisting of chemokine, a defensine, a leukotriene, a formyl-peptide or combinations thereof as well as mutants and/or variants of the chemoattractant.  
     
     
         7 . The method of  claim 1  wherein the compound is selected from the group consisting of R 1 -CCL14[10-74], R1-CXCL12[1-67], R1-CXCL12V3I[1-67], R1-CXCL12[2-67], R1-CXCL12V3I[2-67], R1-CXCL12[1-72], R1-CXCL12V3I[1-72], R1-CXCL12[2-72] and R1-CXCL12V3I[2-72] wherein R 1  is a lipophilic, hydrophobic or polar aprotic residue.  
     
     
         8 . The method of  claim 7 , wherein R 1  is any organic residue having up to 50 carbon atoms, which may be substituted by hetero atoms, and which organic residue is branched, unbranched, saturated, unsaturated or combinations thereof.  
     
     
         9 . The method of  claim 8 , wherein R 1  is an aromatic moiety, polyethylenoxid, moiety with 2 to 18 units, comprising residue.  
     
     
         10 . The method of  claim 7 , wherein R 1  is any amino acid, or CH 3 —(CH 2 ) n —X; in which 
 (CH 2 ) n  is branched or unbranched    X is —C(O)—NH—CH 2 —C(O)—, —NHCH 2 —C(O)—, —ONH—CH 2 —C(O)—, —OCH 2 —CH 2 -C(O)—, —CH═CH—C(O)—, —C(O)—, or a covalent bond;    and n is an integer of 1-17;    or pharmaceutically acceptable salt thereof.    
     
     
         11 . A method of treating a disease state in mammals that is alleviated by treatment with a compound of  claim 7 , which method comprises administering to an mammal in need of such a treatment a therapeutically effective amount of the compound.  
     
     
         12 . The method of  claim 5  wherein said method inhibits inflammation.  
     
     
         13 . The method of  claim 12 , wherein inflammation is selected from the group consisting of allergic asthma, atopic dermatitis, rheumatoid arthritis, and combinations thereof.  
     
     
         14 . Use of an agonist specific for receptor involved with migration of blood circulating cells from the blood stream for the manufacturing of a medicament for the treatment of diseases associated with migration of blood cells from the blood stream into tissues.  
     
     
         15 . Use according to  claim 14  wherein the agonist is a chemo-attractant.  
     
     
         16 . Use according to  claim 14  wherein the chemo-attractant is selected from the group consisting of chemokine, defensin, leukotriene, formyl-peptides as well as mutants and/or variants of the chemo-attractants.  
     
     
         17 . Use of a compound of the method of  claim 7  for the manufacturing of a medicament for the treatment of diseases associated with migration of blood cells from the blood stream into tissues.  
     
     
         18 . A compound R 1 -CCL14[10-74], wherein R 1  is a lipophilic, hydrophobic or polar aprotic residue.