Sublingual immunotherapy.
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Administration, Sublingual↗
Biomedical subjects
Chris Corrigan
Publications and source records attributed to Chris Corrigan.
Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity.
Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines. We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (thymus and activation-regulated chemokine (TARC)/CCL17, macrophage-derived chemokine (MDC)/CCL22, I-309/CCL1) and Th1-attracting (IFN-gamma-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T cell alpha-chemoattractant (I-TAC)/CXCL11) chemokines and expression of their receptors CCR4, CCR8, and CXCR3 in bronchial biopsies from 20 asthmatics and 15 normal controls. The numbers of cells within the bronchial epithelium and submucosa expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly increased in asthmatics as compared with controls (p </= 0.018). TSLP and TARC/CCL17 expression correlated with airway obstruction. Although the total numbers of cells expressing CCR4, CCR8, and CXCR3 did not significantly differ in the asthmatics and controls, there was evidence of selective infiltration of CD4(+)/CCR4(+) T cells in the asthmatic biopsies which correlated with TARC and MDC expression and airway obstruction. Epithelial cells, endothelial cells, neutrophils, macrophages, and mast cells were significant sources of TSLP and chemokines. Our data implicate TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10 in asthma pathogenesis. These may act partly through selective development and retention, or recruitment of Th2 cells bearing their receptors.
Adult↗
Expression of the cysteinyl leukotriene receptors cysLT(1) and cysLT(2) in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis.
BACKGROUND: Cysteinyl leukotrienes play a disease-regulating role in rhinosinusitis and asthma, particularly aspirin-sensitive disease. They act through 2 G-protein coupled receptors termed cysteinyl leukotriene type 1 receptor (cysLT 1 ) and cysteinyl leukotriene type 2 receptor (cysLT 2 ). We previously compared expression of cysLT 1 on mucosal leukocytes in patients with aspirin-sensitive and aspirin-tolerant rhinosinusitis. OBJECTIVE: To compare expression of cysLT 1 and cysLT 2 on leukocytes, mucus glands, and epithelium in 32 patients with chronic polypoid rhinosinusitis (21 aspirin-sensitive, 11 aspirin-tolerant) and 9 normal controls. METHODS: Total numbers of CD45 + leukocytes, percentages of these cells expressing cysLT 1 or cysLT 2 , and percentages of the total epithelial and glandular areas expressing cysLT 1 or cysLT 2 were measured in sections of nasal biopsies by using immunohistochemistry and image analysis. RESULTS: The percentages of mucosal CD45 + leukocytes expressing cysLT 1 were significantly ( P < .0001) elevated in the aspirin-sensitive but not the aspirin-tolerant patients compared with the controls. In contrast, the percentages of leukocytes expressing cysLT 2 did not differ significantly in the 3 groups. On epithelial and glandular cells, expression of cysLT 2 significantly exceeded that of cysLT 1 in both the patients with rhinosinusitis and the controls ( P < or = .004), although there was no significant difference in the expression of either receptor in the patients with rhinosinusitis (aspirin-sensitive or aspirin-tolerant) and the controls. CONCLUSION: Although cysLT 1 expression predominates on inflammatory leukocytes in patients with aspirin-sensitive rhinosinusitis, the effects of cysteinyl leukotrienes on glands and epithelium may be mediated predominantly through cysLT 2. This has potentially important therapeutic implications.
Adult↗
Expression of prostaglandin E(2) receptor subtypes on cells in sputum from patients with asthma and controls: effect of allergen inhalational challenge.
BACKGROUND: Prostaglandin (PG) E 2 binds to 4 G-protein-coupled receptors designated EP 1 through EP 4 . Although PGE 2 plays an immunomodulatory role in asthma, there is little information on the expression of PGE 2 receptors in this disease. OBJECTIVE: We hypothesized that profiles of E-prostanoid (EP) receptor expression are altered on asthmatic bronchial inflammatory cells in vivo and further altered by allergen challenge in vivo and proinflammatory mediators in vitro. METHODS: The numbers and phenotypes of EP 1-4 immunoreactive induced sputum cells from atopic asthmatics (n = 13; before and 24 hours after allergen inhalational challenge) and normal controls (n = 9; 3 after saline challenge) and EP 1-4 expression on purified blood eosinophils from both groups (n = 4 for each) before and after stimulation with LPS and/or IL-5 in vitro were measured by using single and double immunocytochemistry. RESULTS: Subsets of sputum cells of all phenotypes expressed all 4 EP receptors in both patients with asthma and controls. There were significantly greater numbers of macrophages expressing all 4 EP receptors and increased percentages of macrophages expressing EP 2 and EP 4 in patients with asthma compared with controls. Allergen bronchial challenge of patients with asthma was associated with a selective influx of eosinophils, but the percentages of these and other leukocytes expressing all 4 EP receptors were unchanged. Compared with sputum, only small percentages of peripheral blood eosinophils expressed each receptor, but this was increased by culture with exogenous IL-5 or LPS. CONCLUSION: E-prostanoid receptor expression is increased on airway macrophages of patients with asthma at baseline and may be altered on eosinophils after allergen challenge in vivo in response to inflammatory stimuli.
Adolescent↗
Mechanisms of intrinsic asthma.
PURPOSE OF REVIEW: The phenomenon of intrinsic or nonatopic asthma continues to raise questions about the possible role of IgE-mediated mechanisms in asthma pathogenesis. With the current availability of anti-IgE therapy for asthma, clarification of this issue has never been more timely and relevant. RECENT FINDINGS: This article summarizes recent studies for and against the proposition that IgE-mediated mechanisms play a critical role in asthma pathogenesis. These data comprise epidemiological studies and recent molecular studies, suggesting that IgE synthesis may take place in the bronchial mucosa of patients with nonatopic asthma, despite the fact that allergen-specific IgE is not detectable in the periphery by standard skin prick testing. SUMMARY: At present, available data do not allow a firm conclusion to be made as to whether or not IgE-mediated mechanisms play an obligatory role in asthma pathogenesis. Implications for the future therapy of nonatopic asthma in either case are discussed, as well as some suggestions for further research.
Asthma↗