Analysis of nasal secretions during experimental rhinovirus upper respiratory infections (original) (raw)
Related papers
The pathophysiology of rhinitis V. Sources of protein in allergen-induced nasal secretions
Journal of Allergy and Clinical Immunology, 1991
Allergic rhinitis is characterized by a profuse rhinorrhea in addition to paroxysms of sneezing, nasal congestion, and pruritus. To define better the sources of nasal secretion produced durrng rhinitis, nasal allergen challenges were performed on nine atopic subjects with seasonal rhinitis. A single dose of allergen was sprayed into one side of the nose, and nasal lavages were collected bilaterally for 7 hours. Nasal lavages were assayed for protein (total protein, albumin, lactoferrin, and lysozyme) and mediator (histamine and prostaglandin D,) content. Protein concentrations increased and remained elevated above baseline levels in both ipsilateral and contralateral secretions for up to 3 hours after allergen challenge. The proportion of albumin relative to total protein (the albumin percent) increased on the ipsilateral side, whereas the relative proportions of lactoferrin and lysozyme (the lactoferrin percent and lysozyme percent) increased on the contralateral side. Prostaglandin D, , but not histamine, increased selectively on the ipsilateral side. These data suggest that the ipsilateral protein secretory response is due to allergen-induced mast cell mediator release causing increased vascular permeability, whereas the contralateral protein secretory response is primarily a refiex-induced glandular secretion. (J ALLERGYCLINIMMUNOL 1991;88:33-42.)
Studies on the allergic and nonallergic nasal inflammation
Journal of Allergy and Clinical Immunology, 1988
Nasal lavage after antigenic and nonantigenic nasal stimulation has become an important tool for the study of injlammatory phenomena in the upper airway. Biochemical and cytologic information is relatively easily obtainable, and pharmacologic manipulations can be readily monitored. This article is of several studies aiming toward a more profound understanding of the mechanisms of allergic and nonallergic rhinitis by the use of laboratory-challenge procedures and nasal-lavage techniques. An early and a late reaction are detected clinically in the nose after antigen challenge of allergic individuals. In addition, the sensitivity to antigen significantly increases after the initial challenge, and this phenomenon is not obligatorily linked to the presence of a late-phase reaction (LPR). Inflammatory mediators, mostly mast cell-andlor basophil-derived, are detected in the nasal washes and correlate with the symptomatology in both the early and the late reactions. The allergen-induced LPR is marked by an early influx of eosinophils and, later, basophils and neutrophils. Elevation of major basic protein and histamine, but not prostaglandin D, , is detected during the LPR, giving evidence of active eosinophil and basophil participation. Systemic steroids can effectively suppress the clinical, biochemic, and cellular manifestations of antigen-induced LPR. Topical steroids have a similar effect but are also capable of suppressing the early reaction to antigen. A nonallergic form of rhinitis can be induced in the laboratory by nasal inhalation of dry air at freezing temperatures in individuals who report sensitivity to cold and windy environments. Early and late reactions are also detectable with this stimulus, and the panel of mediators appears to be identical with that of antigen-induced rhinitis, indicating activation of the same cell type(s). This stimulus, however, appears to act through dtflerent mechanisms, since pharmacologic agents that control the allergen response are inactive against cold, dry air (CDA) reactions. Studies on the mechanism of CDA-induced rhinitis have detected elevations in the osmolality of nasal secretions after CDA challenge. This occurs only in CDA-sensitive subjects and not in CDA nonresponders or antigen-challenged allergic individuals. Elevated osmolality correlates with mediator release, suggesting a role of nasal fluid tonicity in mast cell activation. The above pieces of information offer signijicant insight in the mechanisms of allergic and nonallergic intammation of the nose and the upper airways. Reconstitution of that information into a persuasive model of the naturally occurring disease and development of new therapeutic modalities will be our tasks in the future. (J ALLERGY CLIN IMMUNOL 1988;81:782-90.)
Cytokine secretion in nasal mucus of normal subjects and patients with allergic rhinitis
Biomedicine & Pharmacotherapy, 2003
Allergic rhinitis is regulated by the local production and release of several cytokines. The levels of Th2 cytokines IL-4, IL-6, IL-10 and the Th1 cytokine IFN-c were studied in nasal mucus from 30 subjects with allergic rhinitis and 45 non-atopic healthy controls. In this study a sampling technique for collecting nasal mucus, well tolerated by the subjects and with a minimal stimulation of the mucosa, was performed. The cytokine concentrations in nasal mucus samples were detected and quantitated by a new paramagnetic particle-based immunofluorescent assay system more sensitive than the conventional ELISA techniques. The new technique showed reliable values of the measured parameters. The nasal mucus from allergic patients contained significantly higher concentrations of IL-4 (25.5 ± 3.6 pg/ml; P < 0.001) and IL-10 (1300 ± 190 pg/ml; P < 0.05) compared to the nasal mucus from control subjects (15.2 ± 2.3 and 532 ± 28 pg/ml, respectively, for IL-4 and IL-10). No significant modification in IFN-c levels of allergic patients was found when compared to control group (respectively, 19.9 ± 3.3 vs. 25.7 ± 5.1 pg/ml; P > 0.05). Moreover, the allergic patients showed lower levels of IL-6 concentrations in the nasal mucus compared to control subjects (64.8 ± 9.1 vs. 129.0 ± 18.1 pg/ml; P = 0.0099). These data can be interpreted by the hypothesis that in response to environmental allergens there is a preferential Th2 polarity by activated CD4+ T cells and that the cytokines IL-6 and IL-10 have, respectively, an important anti-inflammatory and counterregulatory action in the pathogenesis of allergic rhinitis.
Induction, distribution and modulation of upper airway allergic inflammation in mice
Clinical and Experimental Allergy, 2001
Background To further elucidate mechanisms of human allergic rhinosinusitis, we studied the induction, distribution and modulation of allergen-induced upper airway inflammation in a BALB/c mouse model. Methods Allergic inflammation induced with ovalbumin (OVA) by intraperitoneal (IP) injection in alum was compared to repeated intranasal instillation. The type and distribution of inflammatory cells was compared in the respiratory and olfactory epithelial compartments. Eosinophil distribution was assessed using Scarlet Red stain and a polyclonal antibody recognizing eosinophil major basic protein (MBP). The role of interleukin (IL)-5 in upper airway inflammation was tested by administration of polyclonal anti-IL-5 antibody during the sensitization protocol. Results Unsensitized control mice receiving saline failed to develop upper airway eosinophil infiltration. IP OVA-sensitized mice developed marked upper airway mucosal eosinophil infiltration after aerosol OVA challenge, whereas repeated intranasal instillation of OVA produced qualitatively similar, but less intense eosinophil infiltration. Using either sensitization protocol, eosinophil infiltration was seen in areas of the lower portion of the nasal septum, the floor and the lower lateral walls of the mid-caudal region of the nasal cavity. Immunofluorescence staining for MBP confirmed this distribution of eosinophils but also demonstrated some eosinophils in the maxillary sinuses and in circumscribed regions of the ethmoturbinates. All areas of eosinophil infiltration were lined by respiratory epithelium. The selective infiltration of respiratory but not olfactory epithelium by eosinophils was unassociated with a measurable induction of epithelial ICAM-1 or eotaxin expression. OVA-induced upper airway eosinophil infiltration was found to be IL-5 dependent, since administration of a polyclonal anti-IL-5 antibody (TRFK-5) during OVA sensitization resulted in a marked modulation (80% decrease) in eosinophil infiltration in response to subsequent OVA challenge. Conclusion The mouse upper airway, specifically in areas containing respiratory epithelium, is a target for OVA-induced allergic inflammation. This selective infiltration of respiratory, but not olfactory, epithelium is, in part, dependent upon IL-5. This model is useful for further dissection of the inflammatory response with genetic manipulations and targeted immunological approaches.
Vascular Pharmacology, 2005
Allergic rhinitis is a common disease characterized by the symptoms of pruritus, sneezing, hypersecretion and nasal blockage. Increased mucosal barrier permeability has been suggested to be an indicator for the severity of allergic rhinitis. This study investigates the passage of radiolabelled albumin from the nasal mucosal circulation into the lumen in guinea pigs intraperitoneally sensitized and intranasally challenged with antigen. In order to characterize the allergic rhinitis model, we evaluated a number of potential influencing factors in nasal plasma exudation, including antigen doses, volumes of antigen solution used, and animal position during the nasal lavage, and the conditions of nasal lavage. The number of eosinophils and levels of histamine and leukotriene B 4 in the nasal lavage and eosinophils in the nasal mucosa were determined at the early and late phases after antigen challenge. We also compared the effects of topical nasal treatments for allergic rhinitis on nasal inflammatory responses. Our results demonstrate that, in the guinea pig nasal mucosa, topical challenge with antigens induces plasma exudation and histamine release at the acute-phase reaction, and plasma exudation and eosinophil infiltration at the late-phase reaction. These changes are similar to those reported in human allergic rhinitis. Alterations of nasal plasma exudation, histamine release and eosinophil influx were dependent upon the concentrations and volumes of antigens. An antihistamine inhibited the acute-phase reaction partially, whereas budesonide inhibited effects at the late-phase reaction. We suggest that this model of guinea pig allergic rhinitis with the early and late responses may be useful for high-throughout screening of new drugs.
Journal of Allergy and Clinical Immunology, 1997
We have found that acoustic rhinometry is a reliable means of assessing nasal airway caliber changes during the immediate reaction to nasal allergen challenge of sensitive subjects. Comparison of such changes with symptoms and patterns of mediator release could help in the understanding of mechanisms of immediate and late-phase reactions after allergen challenge and their clinical relevance. Nasal minimal cross-sectional area (MCA) was assessed sequentially for 6 hours after two blinded challenges in random order with pollen antigens and buffer diluent in five sensitive human subjects. Comparisons were made with: (1) symptom scores; (2) olfaction changes; and (3) nasal secretion levels of histamine, tryptase, leukotriene C4, serum albumin (a marker of vascular permeability), lactoferrin (a marker of local glandular secretion), and inflammatory cells in nasal scrapings. In four of five subjects there was a significantly greater decrease in MCA after antigen challenge than after diluent challenge, correlating with the degree of subjective nasal congestion. In two of these four subjects there was a prominent second late-phase decrease in MCA at 3 to 5 hours, whereas the MCA was persistently decreased in an additional subject with accompanying subjective congestion. No significant decrease in olfactory acuity occurred. Levels were significantly higher in nasal secretions obtained after antigen challenge than in those obtained after buffer challenge with histamine (9 +/- 2.7 ng/ml vs 1.2 +/- 0.5 ng/ml; p = 0.04); tryptase (95 +/- 83 ng/ml vs 3 +/- 0.9 ng/ml; p = 0.02), leukotriene C4 (5293 +/- 1385 ng/ml vs 578 +/- 183 ng/ml; p = 0.02), and albumin (123 +/- 9 ng/ml vs 19 +/- 1.6 ng/ml; p = 0.005) but not with lactoferrin (4.6 +/- 1.2 ng/ml vs 4.1 +/- 28 ng/ml; p = not significant). Granulocyte exudation was seen after antigen challenge but not after buffer diluent challenge. However, there was not a precise correlation between decreases in MCA with changes in levels of these mediators in individual subjects. Acoustic rhinometry can quantitatively assess congestion during immediate and late-phase reactions after nasal challenge without significant correlation to the degree of individual inflammatory events assessed.
Analysis of human nasal mucous glycoproteins
American Journal of Otolaryngology, 1984
Human nasal turbLnates were cultured in the presence of 3H-giucosamine, which is incorporated into nasal mucous glycoproteins. Nasal mucous glycoprotein was then characterized biochemically, and the effects of various neurohormones and immunologic stimulation on mucous glycoprotein release were analyzed. Fractionation of nasal mucous glycoprotein by gel filtration chromatography revealed a molecular size range of 2 to 200 • 10 s (as judged by protein markers) but displayed a single, acidic charge, as reflected both in a narrow elution pattern from DEAE-cellulose and a sharp isoelectric focusing point of 2.6. Highly enriched nasal mucous glycoprotein preparations consisted of 80 per cent carbohydrate and 20 per cent protein (by weight) and included enzymatically cleavable carbohydrate side chains with molecular weights of 1,600 to 1,800. Thus, nasal mucous glycoproteins are a family of molecules that express uniform acidic charge characteristics and a wide range of molecular sizes. Cholinergic stimulation of atropineinhibitable muscarinic receptors increased nasal mucous glycoproteln release in a doserelated manner, as did a-adrenergic stimulation. However, 13-adrenergic stimulation did not affect mucous.glycoprotein release. Immunologic stimulation of nasal mast cells by either reversed anaphylaxis or antigen challenge after passive sensitization caused both histamine release and increased mucous glycoprotein release. Thus, nasal turbinates provide an accessible source of tissue for the analysis of nasal mucus secretion and mast cell degranulation and may provide a model for the study of pharmacologic approaches to the universally experienced discomfort of rhinorrhea.