HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Youssef, L. A. Articles by Oliver, J. M. Search for Related Content PubMed PubMed Citation Articles by Youssef, L. A. Articles by Oliver, J. M.

Histamine Release from the Basophils of Control and Asthmatic Subjects and a Comparison of Gene Expression between "Releaser" and "Nonreleaser" Basophils¹

Lama A. Youssef^*, Mark Schuyler, Laura Gilmartin^*, Gavin Pickett, Julie D. J. Bard^*, Christy A. Tarleton^*, Tereassa Archibeque, Clifford Qualls, Bridget S. Wilson^*, and Janet M. Oliver^2,*,

^* Department of Pathology, Department of Medicine, and Cancer Research and Treatment Center, University of New Mexico Heath Sciences Center, Albuquerque, NM 87131

Most human blood basophils respond to FcRI cross-linking by releasing histamine and other inflammatory mediators. Basophils that do not degranulate after anti-IgE challenge, known as "nonreleaser" basophils, characteristically have no or barely detectable levels of the Syk tyrosine kinase. The true incidence of the nonreleaser phenotype, its relationship (if any) to allergic asthma, and its molecular mechanism are not well understood. In this study, we report statistical analyses of degranulation assays performed in 68 control and 61 asthmatic subjects that establish higher basal and anti-IgE-stimulated basophil degranulation among the asthmatics. Remarkably, 28% of the control group and 13% of the asthmatic group were nonreleasers for all or part of our 4-year long study and cycling between the releaser and nonreleaser phenotypes occurred at least once in blood basophils from 8 (of 8) asthmatic and 16 (of 23) control donors. Microarray analysis showed that basal gene expression was generally lower in nonreleaser than releaser basophils. In releaser cells, FcRI cross-linking up-regulated >200 genes, including genes encoding receptors (the FcRI and subunits, the histamine 4 receptor, the chemokine (C-C motif) receptor 1), signaling proteins (Lyn), chemokines (IL-8, RANTES, MIP-1, and MIP-1) and transcription factors (early growth response-1, early growth response-3, and AP-1). FcRI cross-linking induced fewer, and quite distinct, transcriptional responses in nonreleaser cells. We conclude that "nonreleaser" and "cycler" basophils represent a distinct and reversible natural phenotype. Although histamine is more readily released from basophils isolated from asthmatics than controls, the presence of nonreleaser basophils does not rule out the diagnosis of asthma.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health Grants P50-HL58364 (University of New Mexico Asthma Specialized Center of Research) and 5MO1 RR0997 (University of New Mexico General Clinical Research Center).

² Address correspondence and reprint requests to Dr. Janet M. Oliver, University of New Mexico, School of Medicine, Department of Cell Pathology Laboratory, 2325 Camino de Salud, Albuquerque, NM 87131. E-mail address: joliver{at}salud.umn.edu

³ Abbreviations used in this paper: FEV₁, forced expiratory volume in one second; Egr, early growth response; HRF, histamine-releasing factor; TCTP, translationally controlled tumor protein; VEGF, vascular endothelial growth factor.