Association of the Src homology 2 domain-containing inositol 5' phosphatase (SHIP) to releasability in human basophils.
During the study of the biology of the Human recombinant Histamine Releasing Factor (HrHRF), we uncovered a hyperreleasable phenotype of basophils from HrHRF-responder donors. Basophils from these donors released histamne to HrHRF, IL-3 and D(2)O. While there has been a significant amount of work elucidating signal transduction events in human basophils, the reason for this hyperreleasable phenotype remained illusive. A clue to the releasability of these highly allergic, asthmatic HrHRF-responder donor basophils was demonstrated in studies using SHIP knockout mice. Bone marrow-derived mast cells from the SHIP knockout mice demonstrated hyperreleasability to stimuli through the IgE receptor and alteration of subsequent signal transduction events. We have demonstrated a highly significant negative correlation between the amount of SHIP protein per cell equivalent and maximum histamine release to HrHRF. These results provide a clue to the hyperreleasable phenotype and implicate SHIP as an additional regulator of secretion in human basophils.
MacDonald
Susan M
SM
The Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. smacdona@jhmi.edu
Vonakis
Becky M
BM
D001491:Basophils / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000502:physiology; D006636:Histamine Release; D006801:Humans; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D015398:Signal Transduction; D000090324:Tumor Protein, Translationally-Controlled 1
D014408:Biomarkers, Tumor; D000090324:Tumor Protein, Translationally-Controlled 1; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases