Autonomous regulation of IgE-mediated mast cell degranulation and immediate hypersensitivity reaction by an inhibitory receptor CD300a

• Published in: Journal of allergy and clinical immunology Vol. 144; no. 1; pp. 323 - 327.e7
• Main Authors: Wang, Yaqiu, Nakahashi-Oda, Chigusa, Okayama, Yoshimichi, Shibuya, Akira
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2019; Elsevier Limited
• Subjects: Anaphylaxis; Animal tissues; Animals; Antigens; Cell culture; Cell Degranulation; Cells, Cultured; Degranulation; Efficiency; Female; Flow cytometry; Humans; Hypersensitivity; Hypersensitivity, Immediate; Immunoglobulin E; Immunoglobulin E - physiology; Induced polarization; Internet; Ionomycin; Localization; Low concentrations; Mast Cells - physiology; Mice; Mice, Knockout; Microscopy; Milk fat globule membranes; Phosphatidylserines - physiology; Receptors, Immunologic - genetics; Receptors, Immunologic - physiology; Software
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2019.03.005

[...]even in the low concentrations of BMMCs in the culture, in which trans-interactions of CD300a with PS were unlikely, Cd300a−/− BMMCs still showed increased degranulation compared with WT BMMCs (see Fig E2, D and E). Interestingly, FcεRI stimulation also induced polarization of FcεRI and colocalization of FcεRI with CD300a and PS (see Fig E2, G and H). [...]the same spatiotemporal localization of CD300a, PS, and FcεRI on MCs might cause CD300a-mediated suppression of FcεRI-mediated, but not ATP- or ionomycin-mediated, CD107a expression during degranulation. Similar results were also observed when mice were intraperitoneally injected with a neutralizing anti-CD300a antibody (EX42) (Fig 2, G), suggesting that the CD300a-PS interaction suppressed PSA. [...]polarized PS was detected only in MCs, rather than at regions surrounding MCs, in the ear tissue of mice after injection with Flag-tagged MFG-E8-D89E (milk fat globule-EGF factor 8 protein- D89E) together with TNP-OVA (see Fig E4 in this article's Online Repository at www.jacionline.org). [...]by combining imaging and functional analyses of MC degranulation, we revealed the physical and functional associations of externalized PS with CD300a via cis-interaction on viable MCs during degranulation (see Fig E5 in this article's Online Repository at www.jacionline.org).