Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia.
Eotaxin is an eosinophil-specific chemoattractant that has been recently identified in rodent models of asthma and host response against tumors. To determine whether a similar molecule might play a role in human inflammatory diseases characterized by eosinophilia, we isolated the human eotaxin gene. We demonstrate that human eotaxin is an early response gene of cytokine-stimulated epithelial and endothelial cells, and is induced in peripheral blood eosinophils by interleukin-3. Eotaxin is directly chemotactic for eosinophils, but not mononuclear cells or neutrophils. Eotaxin messenger RNA accumulates markedly in the lesions of patients with inflammatory bowel disease (ulcerative colitis and Crohn's disease), but not in the lesions of patients with diverticulitis. These results now provide a mechanism involving eotaxin to explain the eosinophil infiltration seen in a variety of human disease; as such, an eotaxin antagonist may be a novel therapy for certain human diseases characterized by tissue eosinophilia.
Garcia-Zepeda
E A
EA
Infectious Disease Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Rothenberg
M E
ME
Ownbey
R T
RT
Celestin
J
J
Leder
P
P
Luster
A D
AD
D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D004802:Eosinophilia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004804:Eosinophils / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008969:Molecular Sequence Data; D016415:Sequence Alignment
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D007377:Interleukin-3