CD300a is expressed on human basophils and seems to inhibit IgE/FcεRI‐dependent anaphylactic degranulation

Abstract

Background. The final response that leads to basophil degranulation results from a cross-talk between activatory and inhibitory signals. However, in the context of basophil biology, the inhibitory mechanisms that control these processes are still poorly understood.Aim. To investigate the expression and function of the inhibitory receptor CD300a in human basophils. Methods. Peripheral blood of 20 patients with birch pollen allergy and 10 healthy control individuals were assessed for CD300a expression before and after activation. To study the function of CD300a, basophils were pre-incubated with anti-human CD300a/c monoclonal antibodies and analyzed for the upregulation of the activation marker CD203c and appearance of the degranulation marker CD63 following IgE-dependent and IgE-independent triggering.Results. Basophils from allergic individuals constitutively expressed significantly less CD300a than non-allergics (P 5 0.001). However, after cross-linking with either anti-IgE or recombinant major birch pollen allergen (rBet v 1), basophils from allergic patients demonstrated a significant and rapid (3 min) up-regulation of CD300a expression in all activated basophils that persisted for over 2 h (P < 0.05). Moreover, CD300a expression was significantly higher in the CD203c bright1 CD63 bright1 subpopulation than in CD203c bright1 CD63 2 cells (P < 0.05). In both patients and controls, pre-incubation with antiCD300a/c significantly inhibited IgE-mediated CD63 expression (P < 0.05), though it did not affect CD203c. In contrast, IgE-independent basophil activation was not inhibited by CD300a/c engagement.Conclusion. CD300a is expressed on human peripheral blood basophils and rapidly up-regulated upon cross-linking of IgE/FceRI and suppresses anaphylactic degranulation. V C 2011 International Clinical Cytometry Society

Mechanism of phosphatidylserine inhibition of IgE/FcεRI-dependent anaphylactic human basophil degranulation via CD300a

“…Preincubation with anti-CD300a alone did not result in any significant effect on basophil activation markers (data not shown). This is not in contrast with our previous study, 5 in which a CD300a receptor-activating antibody (clone MEM-260) was used, resulting in an inhibition of CD63 upregulation. Similarly, preincubating the cells with recombinant human Annexin V reversed the magnitude of aPBMC-induced inhibition up to 82% (Fig 2, B and D; P 5 .04).…”

“…4 The inhibitory receptor CD300a (IRp60) is constitutively expressed on human basophils and rapidly upregulated in response to IgE/FcεRI cross-linking; its engagement selectively suppresses AND without a significant effect on CD203c. 5 Moreover, recently CD300a has been shown to be a receptor for phosphatidylserine (PS) and phosphatidylethanolamine expressed on the membrane of apoptotic cells. 6 This study aimed at investigating the effect of PS recognition by CD300a on IgE/FcεRI-dependent basophilic activation.…”

“…The externalization of PS in the absence of apoptosis as a consequence of granular membrane fusion with the cell membrane involving inversion of membrane leaflet polarity 8 and upregulation of the inhibitory receptor CD300a during basophilic degranulation 5 on a single cell level may contribute to self-terminating mechanisms through cis recognition.…”

The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine

“…Naive B cells express low levels of CD300a, whereas memory B cells and plasma cells express variable levels, and germinal center B cells are negative for CD300a cell surface expression (16). In the myeloid lineage, CD300a is detected on the surface of plasmacytoid dendritic cells (pDCs), myeloid dendritic cells (mDCs), monocytes, macrophages, neutrophils, eosinophils, basophils, and mast cells (13,(18)(19)(20)(21)(22)(23)(24)(25).…”

Mast cells and basophils are essential for allergies: mechanisms of allergic inflammation and a proposed procedure for diagnosis

“…However, the expression of CD117 on some hematopoietic stem cells, melanocytes, and Cajal cells of the gastrointestinal tract, and kit-positive tumors [142] complicates the use of this receptor as a selection marker for mast cells and basophils. CD300a is expressed on human peripheral blood basophils and rapidly upregulated upon IgE/FcεRI cross-linking, showing potential as an activation marker for basophils [143] .…”