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Relationship between spleen tyrosine kinase and phosphatidylinositol 5' phosphatase expression and secretion from human basophils in the general population.
J Allergy Clin Immunol 2007; 119(3):626-33JA

Abstract

BACKGROUND

Previous studies have suggested that expression levels of spleen tyrosine kinase (syk) or phosphatidylinositol 5' phosphatase (SHIP) may explain certain extreme human basophil phenotypes.

OBJECTIVE

This study is designed to explore whether variability in syk and SHIP expression levels in the general population, alone or in concert, can account for the variability in basophil function.

METHODS

A survey of maximum responsiveness to IgE-mediated stimulation, sensitivity, and expression levels of 6 early signaling elements was performed on 36 subjects' basophils.

RESULTS

Of the 6 signaling elements, only syk and SHIP showed a correlation with maximum histamine release or cellular sensitivity. In a multiple regression, syk and SHIP together could account for 67% of population variance, although most of the variance was explained by syk expression. The pattern of expression variance syk>>SHIP1>SHIP2 approximately lyn approximately p85 approximately cbl suggested a process that primarily modulated syk levels. IL-3 is known to modulate syk levels, but we found that a 3-day incubation with IL-3 resulted in increased expression of other signaling elements to a greater degree: cbl>SHIP1>SHIP2 approximately lyn approximately p85 > or = syk, opposite the pattern in the population survey. In contrast, 18-hour stimulation with anti-IgE antibody led to marked downregulation of syk expression, modest downregulation of Fc epsilon RI expression, weak downregulation of lyn expression, and no effect on 23 other signaling elements.

CONCLUSION

Unlike studies in mice, we conclude that expression of syk is a good preconditioning predictor of basophil function in the general population.

CLINICAL IMPLICATIONS

The finding that expression of syk levels may strongly influence functional responses of basophils suggests a mechanism underlying the severity of atopic diseases.

Authors+Show Affiliations

Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA. dmacglas@jhmi.edu

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17336612

Citation

MacGlashan, Donald W.. "Relationship Between Spleen Tyrosine Kinase and Phosphatidylinositol 5' Phosphatase Expression and Secretion From Human Basophils in the General Population." The Journal of Allergy and Clinical Immunology, vol. 119, no. 3, 2007, pp. 626-33.
MacGlashan DW. Relationship between spleen tyrosine kinase and phosphatidylinositol 5' phosphatase expression and secretion from human basophils in the general population. J Allergy Clin Immunol. 2007;119(3):626-33.
MacGlashan, D. W. (2007). Relationship between spleen tyrosine kinase and phosphatidylinositol 5' phosphatase expression and secretion from human basophils in the general population. The Journal of Allergy and Clinical Immunology, 119(3), pp. 626-33.
MacGlashan DW. Relationship Between Spleen Tyrosine Kinase and Phosphatidylinositol 5' Phosphatase Expression and Secretion From Human Basophils in the General Population. J Allergy Clin Immunol. 2007;119(3):626-33. PubMed PMID: 17336612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relationship between spleen tyrosine kinase and phosphatidylinositol 5' phosphatase expression and secretion from human basophils in the general population. A1 - MacGlashan,Donald W,Jr Y1 - 2006/11/13/ PY - 2006/05/16/received PY - 2006/07/05/revised PY - 2006/09/28/accepted PY - 2007/3/6/pubmed PY - 2007/4/14/medline PY - 2007/3/6/entrez SP - 626 EP - 33 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 119 IS - 3 N2 - BACKGROUND: Previous studies have suggested that expression levels of spleen tyrosine kinase (syk) or phosphatidylinositol 5' phosphatase (SHIP) may explain certain extreme human basophil phenotypes. OBJECTIVE: This study is designed to explore whether variability in syk and SHIP expression levels in the general population, alone or in concert, can account for the variability in basophil function. METHODS: A survey of maximum responsiveness to IgE-mediated stimulation, sensitivity, and expression levels of 6 early signaling elements was performed on 36 subjects' basophils. RESULTS: Of the 6 signaling elements, only syk and SHIP showed a correlation with maximum histamine release or cellular sensitivity. In a multiple regression, syk and SHIP together could account for 67% of population variance, although most of the variance was explained by syk expression. The pattern of expression variance syk>>SHIP1>SHIP2 approximately lyn approximately p85 approximately cbl suggested a process that primarily modulated syk levels. IL-3 is known to modulate syk levels, but we found that a 3-day incubation with IL-3 resulted in increased expression of other signaling elements to a greater degree: cbl>SHIP1>SHIP2 approximately lyn approximately p85 > or = syk, opposite the pattern in the population survey. In contrast, 18-hour stimulation with anti-IgE antibody led to marked downregulation of syk expression, modest downregulation of Fc epsilon RI expression, weak downregulation of lyn expression, and no effect on 23 other signaling elements. CONCLUSION: Unlike studies in mice, we conclude that expression of syk is a good preconditioning predictor of basophil function in the general population. CLINICAL IMPLICATIONS: The finding that expression of syk levels may strongly influence functional responses of basophils suggests a mechanism underlying the severity of atopic diseases. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/17336612/Relationship_between_spleen_tyrosine_kinase_and_phosphatidylinositol_5'_phosphatase_expression_and_secretion_from_human_basophils_in_the_general_population_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(06)02016-1 DB - PRIME DP - Unbound Medicine ER -