Chemorepulsion of cells

Abstract

The present invention provides compositions and methods of controlling the direction and/or movement of migratory cells. Specifically, the invention is directed to the identification of novel chemorepellents and unimodal fugetaxins, their agonists and antagonists which alter or affect the movement of cells involved in immune, inflammatory or cancerous phenotypes.

1 . A method of inducing negative chemotaxis in human migratory cells comprising contacting said human migratory cells with a validated chemorepellent. 
     
     
         2 . The method of  claim 1  wherein the human migratory cells are immune cells selected from the group consisting of neutrophils, CD4+ and CD8+ T cells, B cells, monocytes or dendritic cells. 
     
     
         3 . The method of  claim 2  wherein the validated chemorepellent is selected from the group consisting of carbohydrate binding proteins, serpins, bacterial cell wall components, heat shock proteins, natural products, Toll-like receptor ligands, viral factors, semaphorins, elastase inhibitors, antibiotics, muscle cell proteins, plant cell wall components and chemokines. 
     
     
         4 . The method of  claim 3  wherein the immune cells are neutrophils, the validated chemorepellent is a carbohydrate binding protein and wherein said carbohydrate binding protein is galectin-1. 
     
     
         5 . The method of  claim 3  wherein the immune cells are neutrophils, the validated chemorepellent is a serpin and wherein said serpin is antithrombin III. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 3  wherein the immune cells are neutrophils, the validated chemorepellent is a natural product and wherein said natural product is reservatrol. 
     
     
         9 . The method of  claim 3  wherein the immune cells are neutrophils, the validated chemorepellent is a Toll-like receptor ligands and wherein said Toll-like receptor ligand is  E. coli  K12 LPS. 
     
     
         10 . The method of  claim 3  wherein the immune cells are neutrophils, the validated chemorepellent is a viral factor and wherein said viral factor is rvCMVUL146. 
     
     
         11 . The method of  claim 3  wherein the immune cells are neutrophils, the validated chemorepellent is a semaphorin and wherein said semaphorin is semaphorin 3A. 
     
     
         12 . The method of  claim 3  wherein the immune cells are neutrophils, the validated chemorepellent is an elastase inhibitor and wherein said elastase inhibitor is elafin. 
     
     
         13 . The method of  claim 3  wherein the immune cells are neutrophils, the validated chemorepellent is a muscle cell proteins and wherein said muscle cell proteins is tropomyosin. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 3  wherein the immune cells are neutrophils, the validated chemorepellent is an antibiotic and wherein said antibiotic is erythromycin. 
     
     
         16 . The method of  claim 2  wherein the validated chemorepellent has a repellent index greater than 2. 
     
     
         17 . The method of  claim 16  wherein the validated chemorepellent has a repellent index greater than 5. 
     
     
         18 - 22 . (canceled) 
     
     
         23 . A method of inducing negative chemotaxis in human eosinophils comprising contacting said human eosinophils with a chemorepellent, said chemorepellent selected from the group consisting of galectin-1, galectin-2, heat shock protein 27, heat shock protein 40, heat shock protein 47, heat shock protein 70, heat shock protein 90, Pam3CSK4, HKLM (heat killed  L. monocytogenes ), Poly(I:C), FLS-1, imiquimod, paclitaxel, Lipid A Diphos,  P. gingavalis  LPS, Lipomannan  M. smegmatis,  LTA Staph, Standard LTA from  S. aureus,  N-acetylmuramyl (MDP), cathespin G, resveratrol and quercetin dehydrate. 
     
     
         24 . A method of ameliorating an inflammatory response in a subject comprising:
 a. identifying a subject having undergone an inflammatory insult or stimulus, and   b. contacting said subject with a validated chemorepellent at a site of inflammatory response to said inflammatory insult or stimulus in an amount effective to induce negative chemotaxis of at least a portion of a population of immune cells which comprise said inflammatory response.   
     
     
         25 . The method of  claim 24  wherein said population of immune cells are neutrophils. 
     
     
         26 . The method of  claim 24 , wherein the validated chemorepellent is resveratrol.