Eotaxin: eosinophil chemotactic cytokine

Abstract

A chemoattractant protein called “eotaxin” is capable of attracting eosinophils and of inducing eosinophil accumulation and/or activation in vitro and in vivo. Various types of agents that inhibit or otherwise hinder the production, release or activity of eotaxin may be used therapeutically in the treatment of asthma and other inflammatory diseases.

1 . An isolated chemoattractant protein capable of attracting eosinophils and of inducing eosinophil accumulation and/or activation in vitro and in vivo consisting of or comprising an amino acid sequence having at least 40% homology with the amino acid sequence set out in SEQ ID NO: 1 or SEQ ID NO: 2.  
     
     
         2 . A chemoattractant protein as claimed in  claim 1 , having at least 40% homology with the amino acid sequence set out in SEQ ID NO: 2.  
     
     
         3 . A chemcattractant protein as claimed in  claim 1 , consisting of or comprising an amino acid sequence as set out in SEQ ID NO: 1 or SEQ ID NO: 2.  
     
     
         4 . A chemoattractant protein capable of attracting eosinophils and of inducing eosinophil accumulation and/or activation in vitro and in vivo, which is a polypeptide or peptide fragment of a chemoattractant protein as claimed in  claim 1 .  
     
     
         5 . A process for the production of a chemoattractant protein as claimed in  claim 1 , which comprises obtaining bronchoalveolar lavage fluid or an inflamatory exudate from a human or a non-human animal challenged with a provoking stimulus, and isolating a fraction that demonstrates eosinophil chemcattractant activity in vitro and in vivo.  
     
     
         6 . A process for the production of a chemoattractant protein as claimed in  claim 1 , which comprises culturing in vitro macrophages, lymphocytes, neutrophils, mast cells, airway epithelial cells, connective tissue cells, vascular endothelial cells or eosinophils obtained from a human or a non-human animal, and isolating from the cells or from the cell culture fluid a fraction that demonstrates eosinophil chemoattractant activity in vitro and in vivo.  
     
     
         7 . A chemoattractant protein as claimed in  claim 1  obtained by chemical synthesis or by recombinant DNA technology.  
     
     
         8 . An agent that inhibits or otherwise hinders the production, release or action of a chemoattractant protein as claimed  claim 1  the agent being other than RANTES.  
     
     
         9 . An agent as claimed in  claim 8 , which is a receptor for the chemoattractant protein, an antagonist for the chemoattractant protein at a receptor for that protein, or an agent that inhibits the agonist that binds to or activates a receptor for the chemoattractant protein.  
     
     
         10 . An agent as claimed in  claim 9 , which is a receptor for the chemoattractant protein.  
     
     
         11 . An agent as claimed in  claim 9 , wherein the receptor antagonist or the agonist inhibitor is a polypeptide in which the sequence of the full-length naturally occurring chemoattractant protein has been modified by amino acid substitution, or is a polypeptide or peptide fragment comprising part of the amino acid sequence of the naturally-occurring chemoattractant protein and retaining the capability of attracting eosinophils and of inducing eosinophil accumulation and/or activation in vitro and in vivo, or is a polypeptide or peptide fragment comprising part of the amino acid sequence of the naturally-occurring chemoattractant protein, which sequence has been modified by amino acid substitution.  
     
     
         12 . An agent as claimed in  claim 9 , wherein a receptor antagonist is a chemotactic cytokine that binds to the same receptor as does the chemoattractant protein.  
     
     
         13 . An agent as claimed in  claim 8 , which is an antibody against the chemoattractant protein.  
     
     
         14 . An agent as claimed in  claim 8 , for use as a medicament.  
     
     
         15 . A method for making a pharmaceutical preparation for treating asthma or another inflammatory disease comprising admixing an agent that inhibits or otherwise hinders the production, release or action of a chemoattractant protein as claimed in  claim 1  with a pharmaceutically acceptable carrier.  
     
     
         16 . A pharmaceutical preparation which comprises, as active ingredient, an agent as claimed in  claim 8 , in admixture or conjunction with a pharmaceutically suitable carrier.  
     
     
         17 . A method of treating asthma and other inflammatory diseases, comprising the administration of an effective amount of an agent that inhibits or otherwise hinders the production, release or action of a chemoattractant protein as claimed in  claim 1 .  
     
     
         18 . A method of treating asthma and other inflammatory diseases, comprising the administration of an effective amount of an agent that inhibits or otherwise hinders the production, release or action of a chemoattractant protein as claimed in  claim 9 .  
     
     
         19 . An immunoassay for an antigen or other assay for one member of a specific binding pair, characterized in that the antigen or member of the specific binding pair is a chemoattractant protein as claimed in  claim 1 .  
     
     
         20 . An immunoassay for an antibody, characterized in that the antibody is an antibody that forms a complex with a chemoattractant protein as claimed in  claim 1 .  
     
     
         21 . A method of testing a compound for an inhibitory effect on the activity of a chemoattractant cytokine in vitro, characterized in that the chemcattractant cytokine is a chemoattractant protein as claimed in  claim 1 .  
     
     
         22 . A method of determining the ability of a substance to induce eosinophil accumulation and/or activation in vivo, which comprises administering the substance to a test animal previously treated with labelled eosinophils and subsequently determining the number of labelled eosinophils at a skin site.  
     
     
         23 . A method for determining the ability of a substance to inhibit eosinophil accumulation and/or activation induced in vivo by chemoattractant protein as claimed in  claim 1 , wherein to an animal pretreated with labelled eosinophils is administered and the chemoattractant protein and the number of labelled eosinophils at a skin site are subsequently determined.