Polyp formation by experimental tubal occlusion in the rat.

The purpose of this study was to show the early stages of polyp formation, as part of our studies on the pathogenesis of nasal polyps. Two and 4 weeks after experimental tubal occlusion in 18 Wistar rats, 13 showed signs of bacterial infection, respective acute otitis media. In the majority of these rats polypouslike protrusions of the middle ear mucosa were found in whole-mount specimens. All polypouslike protrusions were investigated by cross sections, which revealed localised accumulation of fluid and inflammatory cells in the lamina propria. The polyps were covered with a flattened epithelium, compared to the epithelium in the surroundings. In some of the bigger polyps the apical part was without epithelial covering. The findings suggest that the epithelium by fast polyp growth may be distended and may burst, or that a primary epithelial defect has not been sufficiently covered.     

Epithelial cell proliferation in nasal polyps

The mechanism stimulating the growth of nasal polyps remains unclear. The fact that nasal polyps formation is connected with increase of the epithelial surface suggests that the dysregulation of epithelial cell proliferation takes part in their pathogenesis. Furthermore, macroscopically nonsuspected nasal polyp, usually benign tissue lesion, occasionally may be misdiagnosed such as neoplasm. Only a few studies have undertaken the subject of cell proliferation in nonneoplastic respiratory epithelium. We examined 30 nasal polyps specimens by immunohistochemistry to recognize the expression of nuclear antigen present in proliferating cells, using rabbit anti-human Ki-67 antigen. Our study revealed significantly higher Ki-67 index in nasal polyps than in nasal mucosa (p < 0.005, tab.I). Based on this findings it seems that increased epithelial cell proliferation and chronic inflammation generate the lesion of the nasal mucosa leading to nasal polyps formation.     

Polyp and fibrous adhesion formation in acute otitis media caused by non-typeable or type b Haemophilus influenzae or Moraxella catarrhalis

Among a variety of other histopathologic changes, polyps and fibrous adhesions are readily formed in the middle ear mucosa during experimental acute otitis media (AOM) caused by Streptococcus pneumoniae. Quantitative studies on experimental AOM caused by other bacteria have shown that some of these histopathologic changes, such as adaptive bone modeling and increase in goblet cell density, differ according to the type of bacteria. This investigation surveys polyp and fibrous adhesion formation in experimental AOM caused by either non-typeable or type b Haemophilus influenzae, or Moraxella catarrhalis. Seventy-five rats were inoculated with 1 of these 3 bacteria (25 rats in each of 3 groups). Five rats from each group were sacrificed on days 4, 8, 16, 60 and 180 post-inoculation. The middle ear mucosae were dissected and histopathologic changes in whole-mount and section preparations were studied using light microscopy. Polyps were found in most ears and in the greatest numbers on the early days; fewer polyps were found on the later days, regardless of the type of bacteria. However, non-typeable and type b H. influenzae induced formation of significantly more polyps than M. catarrhalis. The polyps were primarily located in the epitympanum. Fibrous adhesions were primarily located in the hypotympanum and formed in almost all ears, on all days post-inoculation, regardless of the type of bacteria. Numbers increased to a peak on day 16 and then decreased. Non-typeable and type b H. influenzae induced formation of significantly more adhesions than M. catarrhalis, and the middle ears displayed a higher number of persisting adhesions in the animals inoculated with non-typeable H. influenzae. We conclude that polyps and adhesions are formed in experimental AOM regardless of bacterial type, confirming a pathogenesis based on inflammation. Both types of H. influenzae induce formation of greater numbers of polyps/adhesions than M. catarrhalis, and the non-typeable form causes more adhesive sequelae in the mucosa than the encapsulated type b.     

The relationship of nasal polyps, infection, and inflammation

The role of infection as cause or effect in nasal polyps is debated. In experimentally induced sinusitis in rabbits, polyps are frequent. The initial polyp formation sequence involves multiple epithelial disruptions with proliferating granulation tissue. Regenerating epithelial branches spread into the underlying connective tissue, where intraepithelial microcavities give rise to a polyp body from the adjacent mucosa. Clinical as well as experimental studies indicate that nasal polyp formation and growth are activated and perpetuated by an integrated process of mucosal epithelium, matrix, and inflammatory cells, which in turn may be initiated by both infectious and noninfectious inflammation. The complexity of the pathophysiologic events in nasal polyposis is reinforced by the finding that epithelial desquamation, combined with infection or inflammation, will initiate polyp formation. Systemic glucocorticosteroids inhibit polyp formation as well as growth of pathogenic bacteria in the sinuses of rabbits with experimental infection. Therapeutic use of corticosteroids in polyp disease, combined with antibiotics or surgery, should be modified in relation to long-term progression, intensity variations, and predisposing conditions.     

三种基质金属蛋白酶在鼻息肉组织中的表达

目的　探讨三种基质金属蛋白酶 (matrixmetalloproteinases,MMPs)与鼻息肉发病的关系。方法　采用免疫组化法对MMPs成员中MMP2、MMP9及MMP3在 3 2例鼻息肉组织中的表达进行研究。结果　正常鼻粘膜未见有三者的表达 ,鼻息肉组织中MMPs阳性细胞主要位于基底膜附近的细胞。上皮细胞、血液细胞及浸润的炎细胞表达MMP9;成纤维细胞、浸润的炎细胞和上皮细胞表达MMP2 ;少部分上皮细胞和浸润的炎细胞表达MMP3。与正常鼻粘膜相比 ,鼻息肉组织中三者的阳性细胞过度表达 ,三者的阳性细胞表达数比较 ,MMP9明显高于MMP2和MMP3 (P <0 0 1)。结论　MMP2、MMP9及MMP3在鼻息肉组织中过度表达 ,它们可破坏基底膜导致鼻粘膜病理性改变 ,在鼻息肉的发生发展中起到了重要的作用 ,MMP9似乎起到了更重要的作用     

Expression, localization, and significance of vascular permeability/vascular endothelial growth factor in nasal polyps

BACKGROUND: The exact etiologic mechanisms leading to the formation of nasal polyps have remained largely obscure. A key phenomenon of this specific type of chronic inflammatory disease in nasal respiratory mucosa is remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) plays an important role in inducing angiogenesis and modulating capillary permeability. OBJECTIVE: To study the expression and localization of VPF/ VEGF as a putative key factor in nasal polyp development. METHODS: Specimens of nasal polyps (n = 12) were harvested during endonasal sinus surgery in patients with polypous chronic rhinosinusitis. Specimens of healthy nasal respiratory mucosa (n = 12) served as controls and were obtained from inferior turbinates of patients undergoing surgery for nasal obstruction without signs and symptoms of inflammatory disease. Frozen sections were immunohistochemically stained for VPF/VEGF and quantitatively analyzed, using computer-based image analysis. RESULTS: The expression of VPF/VEGF in specimens of nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. CONCLUSION: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. Conclusion: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps.     

Polyp and Fibrous Adhesion Formation in Acute Otitis Media Caused by Non-typeable or Type b Haemophilus influenzae or Moraxella catarrhalis

Among a variety of other histopathologic changes, polyps and fibrous adhesions are readily formed in the middle ear mucosa during experimental acute otitis media (AOM) caused by Streptococcus pneumoniae. Quantitative studies on experimental AOM caused by other bacteria have shown that some of these histopathologic changes, such as adaptive bone modeling and increase in goblet cell density, differ according to the type of bacteria. This investigation surveys polyp and fibrous adhesion formation in experimental AOM caused by either non-typeable or type b Haemophilus influenzae, or Moraxella catarrhalis. Seventy-five rats were inoculated with 1 of these 3 bacteria (25 rats in each of 3 groups). Five rats from each group were sacrificed on days 4, 8, 16, 60 and 180 post-inoculation. The middle ear mucosae were dissected and histopathologic changes in whole-mount and section preparations were studied using light microscopy. Polyps were found in most ears and in the greatest numbers on the early days; fewer polyps were found on the later days, regardless of the type of bacteria. However, non-typeable and type b H. influenzae induced formation of significantly more polyps than M. catarrhalis. The polyps were primarily located in the epitympanum. Fibrous adhesions were primarily located in the hypotympanum and formed in almost all ears, on all days post-inoculation, regardless of the type of bacteria. Numbers increased to a peak on day 16 and then decreased. Non-typeable and type b H. influenzae induced formation of significantly more adhesions than M. catarrhalis, and the middle ears displayed a higher number of persisting adhesions in the animals inoculated with non-typeable H. influenzae. We conclude that polyps and adhesions are formed in experimental AOM regardless of bacterial type, confirming a pathogenesis based on inflammation. Both types of H. influenzae induce formation of greater numbers of polyps/adhesions than M. catarrhalis, and the non-typeable form causes more adhesive sequelae in the mucosa than the encapsulated type b.     

A histological study of formation and growth of nasal polyps

Chronic infection and allergy are considered to be the two major etiologic factors of nasal polyps. Whatever its cause may be, the initial phase of nasal polyp formation is represented by increased exudation from vessels, edema of the lamina propria and the bulging of the nasal mucosa. Nasal polyps were histologically classified into three types: edematous type, glandular and cystic type (ductal type) and fibrous type. Those of the edematous type and the glandular and cystic type are in the active stage of tissue reaction because of permeation of vascular fluid and marked infiltration of round cells. Contrastingly, the fibrous type polyps are in the healing stage of tissue reaction because of marked proliferation of fibroblasts and collagen fibers. The morphological structure of the nasal glands involved in the bulging mucosa determines the type of nasal polyps, whether edematous type or glandular and cystic type.     

三种基质金属蛋白酶在鼻息肉组织中的表达

目的 探讨三种基质金属蛋白酶（ｍａｔｒｉｘ ｅｍｔａｌｌｏｐｒｏｔｅｉｎａｓｅｓ,ＭＭＰｓ）与鼻息肉发病的关系。方法 采用免疫组化法对ＭＭＰｓ成员中ＭＭＰ２、ＭＭＰ９及ＭＭＰ３在３２例鼻息肉组织中的表达进行研究。结果 正常鼻粘膜未见有三者的表达,鼻息肉组织中ＭＭＰｓ阳性细胞主要位于基底膜附近的细胞。上皮细胞、血液细胞及浸润的炎细胞表达ＭＭＰ９;成纤维细胞、浸润的炎细胞和上皮细胞表达ＭＭＰ２;少部分     

Histopathologic differences due to bacterial species in acute otitis media

OBJECTIVE: To compare selected features of histopathology in acute otitis media caused by various bacteria and examine potential differences due to bacterial species, as well as possible correlation to experimental and human clinical findings. METHODS: Rat models of acute otitis media caused by Streptococcus pneumoniae (MC), non-typeable or type b Haemophilus influenzae (NTHI/HIB) or Moraxella catarrhalis (MC) were studied longitudinally up to 6 months after bacterial challenge. Findings related to dynamics of goblet cell density, modeling and remodeling of bone tissue structures and polyp, as well as fibrous adhesion formation and persistence are presented. RESULTS: Middle ear goblet cell density progressed to peak 2 weeks after bacterial inoculation, thereafter gradually normalizing. However, density and accordingly middle ear secretory capacity was still significantly increased after 6 months in all bacteria, except MC. The HI species induced the highest increase. Initial osteoresorption was followed by massive osteoneogenesis, progressing to a peak after 2-3 months, followed by some degree of normalization, concurrently classic remodeling. Primarily SP, but also the HI species induced more new bone formation than MC. Mucosal polyp and fibrous adhesion formation occurred regardless of bacterial species. Most polyps appeared in the early phases and the HI species induced formation of more polyps and adhesions than the other bacteria. CONCLUSION: Acute middle ear infection with the Haemophilus species induce the highest increase of mucosal secretory capacity, lasting for at least 6 months after the acute incident. Thus, a subsequent development of secretory otitis media seems more likely following infection with these bacteria. Equivalently, mucosal scarring observed as polyp and fibrous adhesion formation was more severe following Haemophilus infection. S. pneumoniae induced the most marked changes of bone tissue structures, seen as initial osteoresorption and subsequent osteoneogenesis. Overall, infection with M. catarrhalis induced the mildest changes.     

Significance and expression of transforming growth factor beta in human nasal polyp tissue]

OBJECTIVE: To explore the pathogenesis of nasal polyposis and the expression of transforming growth factor beta (TGF-beta) in human inflammatory nasal polyps. METHODS: TGF-beta 1-3 in nasal polyp tissues and inferior turbinate mucosa of twenty-five polyposis patients were detected with immunohistochemistry alkaline phosphatase and anti-alkaline phosphatase (APAAP) method. The inferior turbinate mucosa of eight healthy volunteers were selected as control. Six polyp tissues were estimated with double immunolabeling and Western-blot analysis to compare the characterization of the TGF-beta isoforms expression and the proportion of macrophages and eosinophils in nasal polyp tissues. RESULTS: The expression of TGF-beta 1-3 in nasal polyps was significantly higher than that in nasal mucosa and indetecable in nasal mucosa from healthy volunteers; TGF-beta 1 was the main isoform detected in nasal polyps; TGF-beta positively was accompanied by numerous macrophage and eosinophil infiltration. CONCLUSIONS: TGF-beta mainly TGF-beta 1 is strongly expressed in nasal polyps and its mucosa, where it could be produced by macrophages and eosinophils. TGF-beta could induce modification of epithelium and connective tissue and therefore be involved in the pathogenesis of nasal polyposis.     

Tenascin在鼻息肉组织中的表达及其临床意义

目的：探讨Tenascin(TN)在鼻息肉组织中的表达和分布特征及其在鼻息肉发生中的可能作用。方法：采用免疫组化链霉菌抗生物素蛋白—过氧化物酶(SP)法检测24例鼻息肉标本(鼻息肉组)和15例慢性肥厚性鼻炎下鼻甲标本(下鼻甲组)中TN的表达，并以5例健康者(对照组)下鼻甲黏膜作对照。结果：鼻息肉组和下鼻甲组黏膜上皮细胞及腺上皮细胞均表达TN；鼻息肉组TN的黏膜上皮阳性细胞表达的吸光度值显著高于下鼻甲组(P＜0．01)；鼻息肉组TN的腺上皮阳性细胞表达的吸光度值显著高于下鼻甲组(P＜0．01)；对照组下鼻甲组织中黏膜上皮及腺体几乎检测不到TN的表达；鼻息肉组腺体TN阳性率明显高于下鼻甲组(P＜0．05)。结论：TN在鼻息肉组织中的高表达与鼻息肉的发生、发展相关；TN在鼻腔内的表达细胞是黏膜上皮细胞和浆液性腺上皮细胞。     

Localization of cystic fibrosis transmembrane conductance regulator in epithelial cells of nasal polyps and postoperative polypoid mucosae

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel protein that plays an important role in electrolyte and water transport through the respiratory epithelial cells. In order to understand the possible role of CFTR in the pathogenesis of nasal polyps and postoperative polypoid mucosae, we aimed to characterize the localization of CFTR in the epithelia of nasal polyps and postoperative polypoid mucosae of subjects who did not manifest the phenotypic expression of cystic fibrosis. Immunohistochemical staining for CFTR, using monoclonal mouse anti-human CFTR, was performed on tissue sections of 4 normal turbinates and nasal polyps and postoperative polypoid mucosae from 10 patients who underwent endoscopic intranasal operations. CFTR showed a typical apical distribution in the normal turbinate mucosae whereas, in the nasal polyps, CFTR demonstrated a heterogenous pattern of localization comprising diffuse or scattered cytoplasmic labelling, very low to undetectable labelling, intense perinuclear staining and intermingled typical apical location. In postoperative polypoid mucosae, the pattern of CFTR localization was less heterogeneous than in the nasal polyp epithelial cells and showed a more prominent feature of diffuse cytoplasmic staining. These results suggest that an altered localization of the CFTR may have a role in the pathogenesis of nasal polyps and postoperative polypoid mucosa.     

Localization of Cystic Fibrosis Transmembrane Conductance Regulator in Epithelial Cells of Nasal Polyps and Postoperative Polypoid Mucosae

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel protein that plays an important role in electrolyte and water transport through the respiratory epithelial cells. In order to understand the possible role of CFTR in the pathogenesis of nasal polyps and postoperative polypoid mucosae, we aimed to characterize the localization of CFTR in the epithelia of nasal polyps and postoperative polypoid mucosae of subjects who did not manifest the phenotypic expression of cystic fibrosis. Immunohistochemical staining for CFTR, using monoclonal mouse anti-human CFTR, was performed on tissue sections of 4 normal turbinates and nasal polyps and postoperative polypoid mucosae from 10 patients who underwent endoscopic intranasal operations. CFTR showed a typical apical distribution in the normal turbinate mucosae whereas, in the nasal polyps, CFTR demonstrated a heterogenous pattern of localization comprising diffuse or scattered cytoplasmic labelling, very low to undetectable labelling, intense perinuclear staining and intermingled typical apical location. In postoperative polypoid mucosae, the pattern of CFTR localization was less heterogeneous than in the nasal polyp epithelial cells and showed a more prominent feature of diffuse cytoplasmic staining. These results suggest that an altered localization of the CFTR may have a role in the pathogenesis of nasal polyps and postoperative polypoid mucosa.     

Cholesterol granulomas in antrochoanal polyps: a clinicopathologic study

The purpose of this study was to investigate antrochoanal polyps with cholesterol granuloma (CG), which is a granulomatous reaction to cholesterol crystals that has been precipitated in the tissue. It is usually associated with chronic middle ear disease, common in the mastoid air cells, less common in the orbit and rarely found in the paranasal sinuses. The aim of this study was to analyze the etiology and pathological findings of antrochoanal polyps associated with cholesterol granuloma. This is a retrospective study of five cases of antrochoanal polyp with cholesterol granuloma, (four males and one female between 15 and 77 years of age) who presented with nasal obstruction, rhinorhea and snoring. The cases were clinically and histologically reviewed. Four patients were treated endoscopically and one by intranasal polypectomy without endoscope. There was no recurrence during the follow-up between 24 to 36 months (mean 31.2 months). Five uncommon cases with antrochoanal polyp with cholesterol granuloma are presented. The cholesterol granulomas consist of fibrous granulation tissue containing cholesterol crystals with surrounding foreign body giant cells. The pathogenesis of antrochoanal polyp with cholesterol granuloma is unclear, and further investigations are needed.