CD66b regulates adhesion and activation of human eosinophils.
Eosinophils and their products are likely important in the pathophysiology of allergic diseases, such as bronchial asthma, and in host immunity to parasitic organisms. However, the mechanisms for proinflammatory mediator release by eosinophils are poorly understood. CD66b (CEACAM8, CGM6, NCA-95) is a single chain, GPI-anchored, highly glycosylated protein belonging to the carcinoembryonic Ag supergene family. CD66b is an activation marker for human granulocytes; however, its biological functions are largely unknown in eosinophils. We found that CD66b is highly expressed on the surface of human peripheral blood eosinophils isolated from healthy individuals. Engagement of CD66b, but not CD66a, by mAb or a natural ligand, galectin-3, activated a Src kinase family molecule, hemopoietic cell kinase (Hck), and induced cellular adhesion, superoxide production, and degranulation of eosinophils. CD66b molecules were localized in lipid rafts, and disruption of lipid rafts or removal of the GPI anchor inhibited the adhesion and activation of eosinophils. Importantly, CD66b was constitutively and physically associated with a beta2 integrin, CD11b, and cross-linking of CD66b induced a striking clustering of CD11b molecules. Thus, CD66b molecules are involved in regulating adhesion and activation of eosinophils, possibly through their localization in lipid rafts and interaction with other cell surface molecules, such as CD11b. Binding of exogenous or endogenous carbohydrate ligands(s) to CD66b may be important in the release of proinflammatory mediators by human eosinophils.
Department of Immunology, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Juhan
J
Yoon
Akihiko
A
Terada
Hirohito
H
Kita
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015550:Cell Degranulation; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects / Q000276:immunology*; D051572:Proto-Oncogene Proteins c-hck / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039481:CD11b Antigen; D018821:CD18 Antigens; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck; D019061:src-Family Kinases