Biological activities of ecalectin: a novel eosinophil-activating factor.
Ecalectin, produced by Ag-stimulated T lymphocytes, is a potent eosinophil-specific chemoattractant in vitro as well as in vivo and thus is implicated in allergic responses. Ecalectin differs structurally from other known eosinophil chemoattractants (ECAs); ecalectin belongs to the galectin family defined by their affinity for beta-galactosides and by their conserved carbohydrate recognition domains. These characteristic features suggest that ecalectin has unique activities associated with allergic inflammation besides ECA activity. Conversely, ecalectin may mediate ECA activity by binding to a receptor of a known ECA via affinity for the beta-galactosides present on this receptor. In this study, we have tested whether ecalectin mediates ECA activity by binding to a receptor of a known ECA, and we have assessed its effects on eosinophils. Ecalectin did not mediate ECA activity by binding to the IL-5R or to CCR3. Also, the ECA activity of ecalectin was mainly chemokinetic. In addition, ecalectin induced concentration-dependent eosinophil aggregation, a marker for eosinophil activation. Ecalectin induced concentration-dependent superoxide production from eosinophils but did not induce degranulation; usually these two events are coupled in eosinophil activation. Moreover, ecalectin directly prolonged eosinophil survival in vitro and did not trigger eosinophils to secrete cytokines that prolong eosinophil survival. These results demonstrate that ecalectin has several unique effects on eosinophils. Therefore, we conclude that ecalectin is a novel eosinophil-activating factor. Presumably, these effects allow ecalectin to play a distinctive role in allergic inflammation.
Matsumoto
Ryoji
R
Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. matsumoto.ryoji@mayo.edu
Hirashima
Mitsuomi
M
Kita
Hirohito
H
Gleich
Gerald J
GJ
D000906:Antibodies / Q000494:pharmacology; D002449:Cell Aggregation; D015550:Cell Degranulation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D037161:Galectins; D006801:Humans; D007700:Kinetics; D037102:Lectins / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology*; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000276:immunology; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000276:immunology; D053649:Receptors, Interleukin-5; D013481:Superoxides / Q000378:metabolism
D000906:Antibodies; C515350:CCR3 protein, human; D002630:Chemotactic Factors; D037161:Galectins; C105032:LGALS9 protein, human; D037102:Lectins; D008222:Lymphokines; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; C022227:eosinophil stimulating promoter; D013481:Superoxides