Induction of Upregulation and Downregulation of the T-Cell Activation Marker CD98 in Patients Undergoing Contrast-Enhanced CT with Iodinated Non-Ionic Dimeric Contrast Medium

OBJECTIVE: This study was designed to determine prospectively the expression of the multifunctional CD98 protein in peripheral white blood cells in patients receiving iodinated contrast media (CM) for a computed tomography (CT) examination. MATERIALS AND METHODS: In 12 adult patients that received non-ionic dimeric CM (iosimenol or iodixanol), the expression of CD98 was analyzed from samples of peripheral white blood cells obtained prior to, one hour, and 24 hours after CM injection by the use of flow cytometry analysis and the use of the direct immunofluorescence technique. RESULTS: Overall, expression of CD98 was significantly downregulated 24 hours after CM injection (51.9% +/- 10.8% vs. 38.8% +/- 16.9%; p < 0.04). Patients that received iosimenol exhibited a more pronounced but not significant decrease of CD98 expression both one hour and 24 hours after CM injection. In an analysis of specific patient responses, CD98 downregulation occurred in eight patients. In two patients, CD98 was upregulated, and in the remaining two patients, expression remained unchanged. No patient acquired an adverse CM reaction. CONCLUSION: This is the first demonstration that CM may be a regulator of CD98 expression. To determine if upregulation is associated with an increased risk for the acquisition of an adverse CM-induced hypersensitivity reaction and if downregulation is associated without a risk for the acquisition of an adverse CM-induced hypersensitivity reaction, further studies with a larger population of patients are required.

CD98 activation increases surface expression and clusteringof beta 1 integrins in MCF-7 cells through FAK/Src- and cytoskeleton-independent mechanisms

CD98, a disulfide-linked 125-kDa heterodimeric type II transmembrane glycoprotein, regulates beta 1 integrin- mediated cell adhesion. However, the molecular mechanisms underlying CD98-mediated activation of beta 1 integrin are presently unclear. In this study, the effects of CD98 signaling on the expression and clustering of beta 1 integrin were investigated. Activation of CD98 augmented surface expression of beta 1 integrin on MCF-7 cells. Cross-linking CD98 induced clustering of beta 1 integrins. Inhibition of phosphorylation of focal adhesion kimase (FAK) by PP2, an inhibitor of Src family kinase, reduced cell-extracellular matrix adhesion, but not surface expression and clustering of beta1 integrin on MCF-7 cells. This result was confirmed by over-expression of dominant negative forms of FAK. In addition, phalloidin or cytochalasin D inhibited CD98-mediated induction of cell-ECM adhesion, but not surface expression and clustering of b1 integrins. The inhibitory effects of PP2, cytochalasin D or phalloidin on CD98-stimulated cell adhesion were diminished by pretreatment of cells with Mn2+, which is shown to induce conformational change of integrins. These results provide the first evidence that CD98 activation increases not only beta1 integrin affinity but also its surface expression and clustering and the latter is independent of FAK/Src and cytoskeleton.

Immunohistochemical analysis of CD71, CD98 and CD99 activation antigens in human palatine and nasopharyngeal tonsils

Tonsils [palatine and nasopharyngeal] are immunologically active tissues. Due to their anatomical location, they are considered to be the initial defense barrier against the antigens entering into the respiratory and gastrointestinal tract. Tonsils act against these antigens by producing and activating the lymphocytes, which are responsible for the immune response. In order to get information regarding the distribution of cell surface antigens on the epithelial, stromal and lymphoid cells of these organs, we performed immunohistochemical staining by using antibodies against CD99, CD71 and CD98 activation antigens. Tissue samples of 20 patients undergoing tonsillectomy and adenoidectomy who presented with recurrent tonsillitis and adenoid hypertrophy in the Otorhinolaryngology Department, Hacettepe University Medical Faculty Hospital, Ankara, Turkey in 2001, were obtained as partial tissue samples apart from pathological examination. Tissues were immunostained by the indirect immunoperoxidase method. Strong CD71 reactivity in macrophages was observed as an indicator of the active role of the macrophages in immunoresponse in the chronic inflammation reaction. The CD98 reactivity on the proliferative basal layer of epithelium was a usual finding, as its detection in epithelial neoplasms and proliferative states is well known. We did not observe any reactivity of CD98 in nasopharyngeal tonsil epithelium and lymphoid cells of either nasopharyngeal or palatine tonsils. The CD99 reactivity was observed in the T-cell dependent area. We determined some topographic difference in the expression of some activation antigens in the epithelial, stromal and lymphoid components of the palatine and nasopharyngeal tonsils. Further detailed studies directed to determine the role of these antigens in tonsils would help to understand the role of these molecules in inflammatory events