Central compartment atopic disease.

BACKGROUND: Isolated polypoid changes of the middle turbinate were recently reported as having a high association with inhalant allergy. A more advanced manifestation of this association may present as polypoid changes of the entire central sinonasal compartment (i.e., the middle and superior turbinates, and the posterosuperior nasal septum), while the lateral sinus mucosa remains relatively normal. OBJECTIVE: To introduce and describe this newly recognized variant of chronic rhinosinusitis (CRS), termed central compartment atopic disease (CCAD). METHODS: A case series of 15 patients from two institutions who presented with sinonasal symptoms and demonstrated central compartment polypoid mucosal changes on computed tomography (CT). The endoscopic appearance of central compartment edema was assessed. Allergy status was determined by skin or serum in vitro testing. RESULTS: The mean ± standard deviation patient age was 42.4 ± 14.8 years, and 47% of the patients were women. All 15 patients had a diagnosis of allergic rhinitis symptomatically, and those who underwent allergy assessment (14/15) tested positive. All the patients had central compartment polypoid edema on endoscopy and central nasal soft-tissue thickening with peripheral clearing on CT. Even with more severe sinus disease, a central focus of inflammatory change existed. CONCLUSION: CCAD may represent a local inhalant allergy process that affects the central nasal structures of ethmoid origin. Although inhalant allergy changes mainly appear within the nasal cavity, medial-to-lateral progression to involve the sinuses can occur as a simple obstructive phenomenon. This is a pattern of CRS distinct from the more diffuse sinonasal inflammatory disease and likely requires allergy management as a core component.

Decellularization of Human Nasal Septal Cartilage for the Novel Filler Material of Vocal Fold Augmentation.

OBJECTIVES: The clinical application of allogenic and/or xenogenic cartilage for vocal fold augmentation requires to remove the antigenic cellular component. The objective of this study was to assess the effect of cartilage decellularization and determine the change in immunogenicity after detergent treatment in human nasal septal cartilage flakes made by the freezing and grinding method. METHODS: Human nasal septal cartilages were obtained from surgical cases. The harvested cartilages were treated by the freezing and grinding technique. The obtained cartilage flakes were treated with 1% Triton X-100 or 2% sodium dodecyl sulfate (SDS) for decellularization of the cartilage flakes. Hematoxylin and eosin stain (H&E stain), surface electric microscopy, immunohistochemical stain for major histocompatibility complex I and II, and ELISA for DNA contents were performed to assess the effect of cartilage decellularization after detergent treatment. RESULTS: A total of 10 nasal septal cartilages were obtained from surgical cases. After detergent treatment, the average size of the cartilage flakes was significantly decreased. With H&E staining, the cell nuclei of decellularized cartilage flakes were not observed. The expression of major histocompatibility complex (MHC)-I and II antigens was not identified in the decellularized cartilage flakes after treatment with detergent. DNA content was removed almost entirely from the decellularized cartilage flakes. CONCLUSION: Treatment with 2% SDS or 1% Triton X-100 for 1 hour appears to be a promising method for decellularization of human nasal septal cartilage for vocal fold augmentation.

Antimicrobial Peptide immunity protects human nasal and auricular cartilage against infection.

BACKGROUND: Despite being impervious to surveillance by the adaptive immune system because of its lack of vascularity, infection of the nasal and auricular cartilage after surgery such as rhinoplasty or otoplasty is rare. Why is this so? Our goal was to determine whether the expression of antimicrobial peptides provides a previously unrecognized nonepithelial layer of innate immune defense within the nasal and auricular cartilage. MATERIALS AND METHODS: Seven samples of nasal septum cartilage and 2 biopsies from auricular cartilage grafts were harvested during rhinoplasty and otoplasty procedures. Ten cadaveric samples of auricular and 9 samples of nasal cartilage were also obtained. Immunohistochemical staining was directed against the human beta-defensin antimicrobial peptides (hBD) 1, 2, and 3. A semiquantitative analysis was performed to measure immunoreactivity. RESULTS: All 3 human beta-defensins were detected along the perichondral line and within the cartilage matrix in the nasal and auricular samples. Areas with positive immunohistochemical staining were also detected within chondrocyte cytoplasm. CONCLUSIONS: We provide the first evidence of antimicrobial peptide expression (hBD-1, -2 and -3) within the perichondrium and cartilage matrix layers of the nasal and auricular cartilage. This previously unrecognized innate immune function of perichondrocytes and chondrocytes may explain the resistance of the nasal and auricular cartilage to infection after surgical procedures despite the absence of a vascular system.

Multiple IgG4-related sclerosing lesions in the maxillary sinus, parotid gland and nasal septum.

IgG4-related sclerosing disease is recognized as a distinct clinicopathological entity. It is well known that this disease can occur in the salivary, lacrimal and pituitary glands, in the head and neck region. The nasal cavity is an extremely rare site of involvement of IgG4-related sclerosing disease. Herein is reported a case of multiple IgG4-related sclerosing lesions in the maxillary sinus, parotid gland and nasal septum. A 73-year-old Japanese man presented with nasal obstruction and tumors of the right maxillary sinus and parotid gland were detected, after which resections of these tumors were performed. One year after the last surgery, he noted swelling of the nasal septum, and the tumor was resected. These three tumors had similar histopathology, such as conspicuous fibrosclerotic changes with dense lymphoplasmacytic infiltration and occasional obliterative phlebitis. Immunohistochemistry indicated abundant IgG4-positive plasma cell infiltration and high ratios of IgG4-positive/IgG-positive plasma cells (>70%) in all three lesions. The diagnosis of multiple IgG4-related sclerosing lesions was made. The present case suggests that IgG4-related sclerosing lesion can occur in the maxillary sinus and nasal septum, and represents an extension of the spectrum of IgG4-related sclerosing disease.

CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice.

PGD(2) is the major prostanoid produced during the acute phase of allergic reactions. Two PGD(2) receptors have been isolated, DP and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), but whether they participate in the pathophysiology of allergic diseases remains unclear. We investigated the role of CRTH2 in the initiation of allergic rhinitis in mice. First, we developed a novel murine model of pollinosis, a type of seasonal allergic rhinitis. Additionally, pathophysiological differences in the pollinosis were compared between wild-type and CRTH2 gene-deficient mice. An effect of treatment with ramatroban, a CRTH2/T-prostanoid receptor dual antagonist, was also determined. Repeated intranasal sensitization with Cry j 1, the major allergen of Cryptomeria japonica pollen, in the absence of adjuvants significantly exacerbated nasal hyperresponsive symptoms, Cry j 1-specific IgE and IgG1 production, nasal eosinophilia, and Cry j 1-induced in vitro production of IL-4 and IL-5 by submandibular lymph node cells. Additionally, CRTH2 mRNA in nasal mucosa was significantly elevated in Cry j 1-sensitized mice. Following repeated intranasal sensitization with Cry j 1, CRTH2 gene-deficient mice had significantly weaker Cry j 1-specific IgE/IgG1 production, nasal eosinophilia, and IL-4 production by submandibular lymph node cells than did wild-type mice. Similar results were found in mice treated with ramatroban. These results suggest that the PGD(2)-CRTH2 interaction is elevated following sensitization and plays a proinflammatory role in the pathophysiology of allergic rhinitis, especially pollinosis in mice.

[The role of protein kinase C and activator protein-1 signal cascade in the regulation of expression of interleukin-5 in T lymphocyte of allergic rhinitis].

OBJECTIVE: To explore the role of protein kinase C (PKC) and activator protein-1 (AP-1) in the signal transduction cascade in the expression of interleukin-5 (IL-5) by peripheral blood T lymphocytes from allergic rhinitis. METHOD: Twenty-five allergic rhinitis patients and twenty-three deflection of nasal septum(DNS) persons in the study. T lymphocytes were isolated and purified from peripheral blood of each person and randomly divided into 3 groups: group A, blank (DNS and AR); group B, PKC excitomotor 12-myristate 13-acetate (DNS PMA and AR PMA); group C , PMA and curcumin (DNS PMA/curcumin and AR PMA/curcumin). ELISA was used to assess the expression of IL-5 in supernatants, and immunocytochemical staining for the activation of AP-1. RESULT: The percentage of cells of active AP-1, IL-5 protein in supernatants of allergic rhinitis T lymphocytes stimulated with PMA were significantly higher than those of allergic rhinitis T lymphocytes stimulated without PMA (P < 0.01) and with PMA and curcumin (P < 0.01); than those of deflection of nasal septum T lymphocytes stimulated with PMA (P < 0.01), with PMA and curcumin (P < 0.01) and without PMA. The percentage of cells of active AP-1, IL-5 protein in supernatants of allergic rhinitis T lymphocytes stimulated with PMA and curcumin were significantly lower than those of allergic rhinitis T lymphocytes stimulated with PMA (P < 0.01); but significantly higher than those of allergic rhinitis T lymphocytes stimulated without PMA and those of deflection of nasal septum T lymphocytes stimulated. There were good positive correlation between the percentage of cells of active AP-1 and IL-5 protein in supernatants (r = 0.92, P < 0.01). CONCLUSION: AP-1 may participate in the signal transduction of PKC-triggered expression of IL-5 in allergic rhinitis T lymphocytes. This suggests the activation of PKC/AP-1 signal transduction cascade of T lymphocytes may play an important role in the pathogenesis of allergic rhinitis.

Concomitant allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis: a review of an uncommon association*.

BACKGROUND: Although thought to have common immunopathological processes, concomitant occurrence of allergic bronchopulmonary aspergillosis (ABPA) and allergic Aspergillus sinusitis (AAS) appears to be rarely reported as to date only five detailed case reports are available. OBJECTIVE: To present a review of seven cases of concomitant ABPA and AAS, three of whom were earlier reported for their unusual presentations. METHODS: Patients with ABPA with nasal symptoms were evaluated radiologically. Consent was taken for antral wash and/or Caldwell-Luc operation in those with radiological evidence of sinusitis and the material was sent for histopathological and mycological studies. RESULTS: Of the 95 patients with ABPA, 22 had radiological evidence of sinusitis. Nine consented to surgery, seven of whom were diagnosed as concomitant AAS. Nasal symptoms preceded chest symptoms in two patients, vice versa in one and occurred simultaneously in four. Familial occurrence of ABPA, middle lobe syndrome and collapse with effusion along with an operated aspergilloma were seen in one patient each. Transient pulmonary infiltrates and central bronchiectasis were seen in all patients. Computed tomography of the paranasal sinuses, carried out in six patients, revealed mucosal thickening with hyperdense lesions, without any bony erosion or destruction. All patients had positive skin tests, positive precipitin study and raised total and specific IgE. Allergic mucin was seen in all patients, fungal hyphae in five, and culture grew Aspergillus spp. in four. All patients responded favourably to oral prednisolone. CONCLUSION: Concomitant occurrence of ABPA and AAS seems to be infrequently recognized. Since asthma and sinusitis are often seen by two different specialities, the occurrence of AAS in ABPA and ABPA in AAS may easily be overlooked.

A new animal model for relapsing polychondritis, induced by cartilage matrix protein (matrilin-1).

Relapsing polychondritis (RP) differs from rheumatoid arthritis (RA) in that primarily cartilage outside diarthrodial joints is affected. The disease usually involves trachea, nose, and outer ears. To investigate whether the tissue distribution of RP may be explained by a specific immune response, we immunized rats with cartilage matrix protein (matrilin-1), a protein predominantly expressed in tracheal cartilage. After 2-3 weeks, some rats developed a severe inspiratory stridor. They had swollen noses and/or epistaxis, but showed neither joint nor outer ear affection. The inflammatory lesions involved chronic active erosions of cartilage. Female rats were more susceptible than males. The disease susceptibility was controlled by both MHC genes (f, l, d, and a haplotypes are high responders, and u, n, and c are resistant) and non-MHC genes (the LEW strain is susceptible; the DA strain is resistant). However, all strains mounted a pronounced IgG response to cartilage matrix protein. The initiation and effector phase of the laryngotracheal involvement causing the clinical symptoms were shown to depend on alphabeta T cells. Taken together, these results represent a novel model for RP: matrilin-1-induced RP. Our findings also suggest that different cartilage proteins are involved in pathogenic models of RP and RA.

[Mast cells and eosinophils of the respiratory mucosa of sheep with Oestrus ovis (Linné, 1761) infection]. / Mastocytes et eosinophiles de la muqueuse respiratoire du mouton infesté par Oestrus ovis (Linné, 1761).

Mast cells and eosinophils have been identified by differential stainings and counted in mucous membrane of nasal septum, turbinates and sinus of 77 ewes naturally infected with Oestrus ovis. Results have been compared with those of nine parasite free lambs. Anova tests indicate significant differences between infected and parasite-free sheep for the cell numbers and their distribution among the septum, the turbinates and the sinus and according to their position in mucous membrane, interglandular chorion of sub-mucosa. In infected sheep, the mean number of mast cells is twice the number present in parasite free animals. The burdens of eosinophils are multiplied by 17 for the septum, 29 for the turbinates and 58 for the sinus. The hypothesis of the development of an hypersensitivity phenomenon in ovine oestrosis is sustained by these results.

The effects of antirat nasal septum cartilage antisera on facial growth in the rat.

Antirat nasal septum cartilage antisera (RNS-IgG) produced in rabbits by injection of crude antigens derived from rat nasal septum cartilage was cytotoxic for rat chondrocytes in vitro. The effect of this antisera on rat facial growth was tested by injecting three groups of growing rats at 4-day intervals from birth to 30 days. The treatment group (n = 19) received injections of RNS-IgG, one control group (n = 11) received injections of the IgG fraction of preimmune rabbit sera (PI-IgG) and a second control group (n = 16) received injections of normal saline. All animals were killed at the conclusion of the experiment, and lateral and dorsoventral cephalometric radiographs were taken. Statistical difference between treatment and control groups were found for 15 cephalometric measurements. Specifically, snout length (as measured from the intersphenoidal synchondrosis to the upper incisors (is-i) was reduced in animals treated with RNS-IgG compared with both PI-IgG and saline injected controls (p < 0.06, p < 0.005, respectively). In addition, premaxillary length, premaxillary displacement, and bimaxillary width were significantly reduced (p < 0.05) in RNS-IgG treated animals compared with saline injected controls. Bimolar width was reduced (p < 0.05) between RNS-IgG and PI-IgG groups. These results demonstrate that injection of antinasal septum antisera reduces midfacial dimensions in experimental rats and that nonimmune rabbit antisera may have an effect on the growth process. In summary, the results of this pilot study suggest the possibility for using more specific antinasal cartilage antibodies to effect dose-dependent, tissue specific, modulation of facial growth.

Differential binding patterns of three antibodies (VOBM1, VOBM2, and VOM2) in the rat vomeronasal organ and accessory olfactory bulb.

Immunohistochemical properties of monoclonal antibodies raised against the rat vomeronasal epithelium were examined in adult rats. Three monoclonal antibodies, VOBM1, VOBM2, and VOM2, reacted specifically to the luminal surface of the sensory epithelium of the vomeronasal organ. In addition, the reactivities of VOBM1 and VOBM2 were detected in the vomeronasal nerve layer and the glomerular layer of the accessory olfactory bulb. Electron-microscopic study revealed differential patterns of the immunoreactivity of the three antibodies to the microvilli of vomeronasal sensory epithelium. VOBM1 immunoreactivity was found on the microvilli of the supporting cells, whereas VOBM2 immunoreactivity was found on those of the sensory cells. VOM2 immunoreactivity was observed on the microvilli of both the sensory and supporting cells. These results suggest that the three antibodies recognize different antigens on the vomeronasal sensory epithelium. In particular, VOBM2 antibody appears to react to an antigen specific to the microvilli of the vomeronasal sensory cells.

Identification of neutrophils in the nonsensory epithelium of the vomeronasal organ in virus-antibody-free rats.

Cells infiltrating the nonsensory epithelium of the vomeronasal organ of virus-antibody-free rats exhibited surface immunoreactivity for beta 2-microglobulin and immunoglobulin (Ig) E. They were further characterized by using immunohistochemical techniques with antibodies to cell-specific markers or histochemical techniques for immunocytes with surface receptors for IgE. Localization of intracellular granules immunoreactive for lactoferrin and CD18, a leukocyte adhesion molecule, unequivocally identified these cells as neutrophils. The low number of IgA- and IgG-immunoreactive B lymphocytes, T lymphocytes, and accessory immunocytes in the vomeronasal organ as well as the rest of the nasal cavity confirmed the absence of infection. We hypothesize that the operation of the vomeronasal pump induces repeated episodes of transient focal ischemia followed by reperfusion, which results in release of neutrophil chemoattractants and modulation of adhesion factors that regulate the extravasation and migration of neutrophils into the nonsensory epithelium. The distribution of immunoreactivity for interleukin 8 suggests that it is not the primary neutrophil chemoattractant in this system while that of CD18 suggests its active involvement in neutrophil extravasation. In addition to their role in immune surveillance, neutrophils may stimulate ion/water secretion into the vomeronasal lumen, affecting the perireceptor processes regulating stimulus access and clearance from the sensory epithelium.

Immunocytochemical study of the differentiation process of the septal organ of Masera in developing rats.

The septal organ of Masera is a small patch of olfactory epithelium located near the base of the nasal septum. Using the growth-associated protein B-50/GAP-43 as neuronal marker, we have studied the differentiation process of this organ from the olfactory sheet in embryonic and newborn rats. Results show that the septal organ first appeared at embryonic day 16. Even though it was included in the olfactory sheet, the presumptive septal organ could be distinguished by a higher density of B-50/GAP-43-positive neurons. Concomitantly to its morphological development, the septal organ progressively isolated from the main olfactory epithelium. This isolation resulted from the extension of a transitional area which progressively lost its typical features of olfactory epithelium to become a putative respiratory epithelium in late embryonic stages. Results strongly suggest that the septal organ should be a proper chemosensory system with its own time-course of development.

Monoclonal antibody (VOM2) specific for the luminal surface of the rat vomeronasal sensory epithelium.

Monoclonal antibodies were raised and selected for reactivity with the luminal surface of the rat vomeronasal organ. Among the monoclonal antibodies generated, the one named VOM2 showed specific immunoreactivity within the luminal surface of the rat vomeronasal sensory epithelium. The VOM2 antigen appeared weakly on the luminal surface at postnatal day 14 (P14). After P21, VOM2 immunoreactivity as strong as that in the adult vomeronasal organ was observed. Immunofluorescence staining using VOM2 antibody showed no reactivity on the luminal surface of the adult mouse or hamster vomeronasal organ. An immunoblotting analysis showed that the VOM2 antigen was a protein with a molecular weight of 24,500.

Antigen presenting cell function of class II positive human nasal chondrocytes.

It is postulated that class II positive chondrocytes may be actively involved in the destruction or rejection of vital transplanted cartilage grafts. To investigate whether human nasal chondrocytes may also function as accessory cells in ongoing immune reactions with cartilage destruction, mixed leukocyte-chondrocyte cultures and antigen presentation assays were performed. Freshly isolated HLA class II antigen negative chondrocytes obtained from nasal septa were not stimulatory to autologous resting T lymphocytes. HLA class II positive chondrocytes treated with gamma-interferon were able to present antigens to autologous activated T cells derived from an antigen (tetanus) specific T cell line. Upon incubation with activated T cells, initially class II negative changed their phenotype resulting in the expression of class II antigens and enabling them to effectively present antigen. These results suggest an active role of chondrocytes in the rejection of cartilage grafts.

Mucosal immunity and protection after intranasal immunization with recombinant adenovirus expressing herpes simplex virus glycoprotein B.

A recombinant adenovirus (Ad) expressing glycoprotein B (gB) of herpes simplex virus (HSV) type 1 (AdgB8) was evaluated as a mucosal vaccine candidate. When administered intranasally (inl) to C57B1/6 mice, AdgB8 induced levels of serum anti-HSV gB IgG antibodies similar to those of mice immunized intraperitoneally (ip), which neutralized both HSV-1 and -2. Mice immunized inl with AdgB8 produced secretory IgA specific for HSV gB, but mice immunized ip did not. Splenic anti-HSV cytotoxic T lymphocytes (CTL) were observed after inl and ip immunization; however, there was a time-dependent decrease in the anti-HSV CTL activity from spleens of inl immunized mice. Anti-HSV CTL were also present in the mediastinal lymph nodes after inl but not ip AdgB8 immunization. Furthermore, mice immunized inl with AdgB8 were protected against heterologous inl challenge with HSV-2, and this protection lasted longer than in ip-immunized mice. These results indicate that mucosal immunization with a recombinant adenovirus can induce mucosal and systemic immune responses and provide long-term protection from mucosally or sexually transmitted viruses.

Characterization of the immune barrier in human olfactory mucosa.

Immunologic defense factors in the human olfactory mucosa were localized immunohistochemically. Olfactory epithelium was identified with an antiserum to olfactory marker protein, specific for olfactory receptor neurons. Constituents of the secretory immune system, including IgA, IgM, secretory component, and J chain, were localized in the acinar and duct cells of Bowman's glands and in the mucociliary complex. In addition, B lymphocytes in the lamina propria near Bowman's glands displayed immunoreactivity for IgA, IgM, and J chain. Immunostaining also localized other humoral factors. Immunoreactivity for IgG was present throughout the stroma and in B lymphocytes in the lamina propria. Antibody to IgD stained numerous B lymphocytes clustered below the basement membrane. Antibody to IgE stained similarly distributed cells; toluidine blue staining demonstrated that many were mast cells. In addition, antibodies to IgD and IgE stained occasional intraepithelial B lymphocytes or mast cells. Two antimicrobial proteins, lactoferrin and lysozyme, were localized in Bowman's glands and the mucociliary complex. Thus, the human olfactory mucosa, which provides a direct neural route for pathogens to the brain, is a site for synthesis and secretion of immune and other defense factors.

Class II antigenicity of human cartilage: relevance to the use of homologous cartilage graft for reconstructive surgery.

The presence and distribution of class II transplantation antigens was studied on fresh and Merthiolate-preserved human nasal, tracheal, auricular, and rib cartilage using monoclonal antibodies in an indirect immunoperoxidase method. Substantial class II antigen expression was found on cells of the superficial area of the perichondrium of the nasal, auricle, and tracheal cartilages. In contrast, cartilage tissue lacked cells with detectable class II antigens. Our results indicate that the host response to fresh cartilage graft is induced by class II antigens presented in the perichondrium. A complete disappearance of this class II antigenicity of perichondrium can be achieved by means of an adequate Merthiolate preservation.