A crucial role for beta 2 integrin in the activation of eosinophils stimulated by IgG.
An IgG-coated surface, such as found on parasites, is one of the most effective physiologic stimuli for eosinophil activation. Recent evidence suggests that cellular adhesion, especially that through the beta 2 integrin, is an important step in cellular activation and accumulation. Therefore, we investigated the role of adhesion molecules in IgG-stimulated eosinophil functions. Cross-linking of eosinophil cytophilic IgG by anti-IgG immobilized to tissue culture plates induced degranulation, whereas soluble anti-IgG did not. Similarly, eosinophils exposed to human IgG immobilized to plates adhered and degranulated; in addition, adherence and subsequent degranulation were inhibited by mAbs to CD18 and CD11b, but not by mAb to CD29, suggesting an important role of beta 2 integrin for these responses. Eosinophil degranulation induced by IgG covalently coupled to Sepharose 4B beads was also inhibited by mAb to CD18. Furthermore, fibrinogen, a ligand for CD11b/18, showed synergistic enhancement of IgG-induced degranulation when it was co-immobilized with IgG to plates. A morphologic study showed that eosinophils, stimulated by immobilized IgG, protrude numerous pseudopods; this morphologic change was inhibited by mAb to CD18. This cellular adhesion seems to affect the early signaling events in eosinophils because the production of inositol phosphates was abolished by mAb to CD18. Interestingly, although superoxide production by eosinophils triggered by immobilized IgG was inhibited by mAb to CD18, superoxide production and morphologic change of neutrophils were not. These results suggest that cell adhesion through CD11b/18 is a crucial step for the activation, signaling, and effector function of eosinophils stimulated by IgG.
Kaneko
M
M
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Horie
S
S
Kato
M
M
Gleich
G J
GJ
Kita
H
H
D000911:Antibodies, Monoclonal / Q000502:physiology; D018821:CD18 Antigens / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology*; D015550:Cell Degranulation / Q000502:physiology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism* / Q000502:physiology*; D007295:Inositol Phosphates / Q000096:biosynthesis; D016023:Integrins / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology; D009195:Peroxidase / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D007074:Immunoglobulin G; D007295:Inositol Phosphates; D016023:Integrins; D013481:Superoxides; D009195:Peroxidase