Objective/Hypothesis To evaluate the histology, RNA and protein signatures of nasal polyps in order to demonstrate specific subtypes of disease and differentiate “idiopathic” NPs based on tissue eosinophilia. Study Design Prospective laboratory based study Methods NP tissue was obtained from patients referred to the University of Virginia Health System for sinus surgery. Histology analyses included hematoxylin-eosin, Gomori's trichrome, toluidine blue, and chloroacetate staining. RNA and protein were extracted from tissue and cytokine transcript or protein concentrations determined. Results Idiopathic NPs can be divided into distinct subsets characterized by absence (NE) and presence (E) of prominent eosinophilia. The validity of this distinction is supported by the demonstration that NE polyps are further distinguished by glandular hypertrophy, dense collagen deposition, and mononuclear cellular infiltrate. In contrast, E-NP display edema, rare glandularity, and minimal collagen deposition except within the basement membrane. Total mast cell numbers were reduced in E-NP, whereas connective tissue mast cells were increased in NE-NP. Consistent with the distinctive pattern of increased fibrosis, NE-NP displayed increased transforming growth factor (TGF)-ß and vascular endothelial growth factor transcripts. Similarly, NE-NPs had higher concentrations of TGF-ß, fibroblast growth factor-ß, and platelet-derived growth factor protein. Conclusion Idiopathic NPs can be distinguished by their presence or absence of eosinophilia and is supported by the observations that these display distinct histological, gene and protein expression patterns. The findings suggest that as unique diseases, idiopathic NPs will require distinct therapeutic interventions.
Arachidonic acid can be metabolized to form a group of compounds known as the cysteinyl leukotrienes (CysLT) that bind to one of two receptors to mediate their actions. On circulating cells, expression of the leukotriene receptors is low, but in inflamed tissue the receptor number is dramatically increased. We hypothesized that the cytokine milieu present during inflammation can increase receptor expression on infiltrating immune cells. Various cell populations were purified from peripheral blood and stimulated in vitro with cytokines characteristic of allergic inflammatory disorders, and CysLT receptor expression was measured using quantitative PCR analysis, Western blot, and flow cytometry. IL-4, but not IL-13, was able to significantly induce mRNA and protein levels for both CysLT receptor 1 and 2 from T cells and B cells. CysLT2 receptor expression was also significantly increased in monocytes and eosinophils after IL-4 stimulation. Surprisingly, CysLT2 receptor expression was increased in monocytes, T cells, and B cells when IFN-␥ was used as the stimulus. Factors involved in eosinophil growth and survival were tested for their ability to alter CysLT receptor expression. These results support the concept that cytokines increase expression of both receptors on lymphocytes and granulocytes, allowing these cells to be more responsive to secreted leukotrienes at sites of inflammation.Keywords: cysteinyl leukotriene receptor; T cell; B cell; eosinophil; cytokine In 1937, the slow-reacting substance of anaphylaxis was described based on the identification of a mediator derived from activated mast cells that, in an antihistamine-resistant fashion, mediated the sustained, prolonged contraction of smooth muscle. This mediator was later identified as a group of compounds known as the cysteinyl leukotrienes (CysLTs). Leukotrienes (LTs) are derived from the metabolism of arachidonic acid. Membrane phospholipids are converted into arachidonic acid by the action of a family of enzymes termed phospholipase A 2 . With cell activation, the enzyme 5-lipoxygenase (5-LO) translocates from the cytosol to the inner nuclear membrane, where in association with 5-lipoxygenase-activating protein (FLAP), it oxygenates and then dehydrates arachidonic acid to generate LTA 4 (1). LTA 4 can be conjugated with the tripeptide glutathione into the cysteinyl leukotriene LTC 4 by the enzyme LTC 4 synthase (LTC 4 S) (or the related enzyme microsomal glutathione (Received in original form July 12, 2006 and in final form January 29, 2007 ) This study was supported by a medical school grant from Merck and Co., PO1 AI50989, AI057438, and AI47737.Correspondence and requests for reprints should be addressed to John W. Steinke, Asthma and Allergic Disease Center, Box 801355, University of Virginia Health System, Charlottesville, VA 22908. E-mail: js3ch@virginia.edu This article has an online supplement, which is accessible from this issue's table of contents at www.atsjournals.org. CLINICAL RELEVANCEThese results show that the inflammatory milieu...
Bacteria of the adenoid reside in secretions on the surface and in crypts. Biofilms, predominantly planktonic, were present on 8 of 9 adenoids excised because of hypertrophy. Whether biofilms have a role in the causation of adenoid hypertrophy is not known.
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