Detection of C5a receptors on human eosinophils and inhibition of eosinophil effector functions by anti-C5a receptor (CD88) antibodies
✍ Scribed by Jörn Elsner; Martin Oppermann; Alexander Kapp
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 561 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Detection of C5a receptors on human eosinophils and inhibition of eosinophil effector functions by anti-C5a receptor (CD88) antibodies
Eosinophils and complement activation are reported to play a crucial role in the pathogenesis of connective tissue diseases. Depositions of antigens and antigenantibody complexes lead to complement activation with the generation of anaphylatoxins, particularly C5a, which is thought to be responsible for the infiltration and activation of eosinophils in the tissue. Previous studies suggested that the eosinophil C5a receptor differs structurally from the receptor expressed on neutrophils. In this study, we investigated the expression and functional properties of C5a receptors on human eosinophils using the CSa receptor monoclonal antibody S5/1 (anti-CD88 mAb). Flow cytometric analysis demonstrated that the anti-CD88 mAb bound homogeneously on the surface of human eosinophils from nonatopic healthy donors. In addition, no subpopulations with respect to C5a receptor expression were identified in normodense or hypodense eosinophils of patients with hypereosinophilia. Pre-incubation of eosinophils with anti-CD88 specifically inhibited C5a-induced intracellular calcium concentration transients. C5a-induced chemotactic activity of eosinophils was significantly inhibited after pre-incubation of cells with antLCD88 mAb in a dose-dependent manner. Furthermore, antLCD88 mAb inhibited dose-dependently the release of reactive oxygen species by eosinophils following stimulation with C5a. Thus, the human eosinophil CSa receptor is homogeneously expressed on normal eosinophils from healthy donors as well as on hypodense and normodense eosino-phi1 subpopulations from patients with hypereosinophilia. Based on the inhibitory effect of the SS/1 mAb on C5a-stimulated eosinophil effector functions, we conclude that a single C5a receptor type exists on human eosinophils. In addition, the inhibitory effect of the S5/1 mAb on C5a functions may enable a new experimental approach to the treatment of diseases that have been associated with CSa-mediated activation.