Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although eosinophils and neutrophils have been identified in orbital and corneoscleral tissues in some patients with Wegener's granulomatosis, their role in the pathogenesis of the disorder is not completely understood. Nine specimens from six patients with Wegener's granulomatosis and autopsy controls from patients without ophthalmic disease were evaluated with indirect immunofluorescence for eosinophil granule major basic protein and neutrophil elastase. Extracellular deposition of both major basic protein and elastase was identified in orbital tissues from all the patients with Wegener's granulomatosis. Two of the specimens were from enucleated eyes with corneoscleral disease; extracellular deposition of eosinophil major basic protein was identified in one eye, and extracellular neutrophil elastase was deposited in both eyes in lesional areas. None of the control tissues showed major basic protein or elastase deposition. These findings suggest that both eosinophils and neutrophils participate in the pathogenesis of the orbital and corneoscleral manifestations of Wegener's granulomatosis.
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PMID:Eosinophil and neutrophil degranulation in ophthalmic lesions of Wegener's granulomatosis. 175 42

To test whether neutrophils infiltrate and degranulate in areas of chronic respiratory allergic inflammation, we developed an indirect immunofluorescence technique to localize neutrophil elastase in formalin-fixed, paraffin-embedded tissues. The affinity-purified antielastase stained only neutrophils on peripheral blood buffy coat smears, and in lung tissue from patients with pneumonia. We examined tissue specimens from four patients with fatal asthma, 10 patients with chronic sinusitis, and 10 patients with nasal polyposis for the presence of elastase, as well as eosinophil granule major basic protein (MBP). Neutrophil infiltration and extracellular elastase deposition in association with damage to respiratory epithelium were generally sparse in most specimens; the exceptions were one patient with asthma, one patient with chronic sinusitis, and two patients with nasal polyposis. In contrast, eosinophil infiltration and extracellular MBP deposition were generally marked in most specimens; the exceptions were one patient with asthma and one patient with nasal polyps where extracellular MBP deposition did not coincide with damage to respiratory epithelium. The results suggest that the neutrophil does not usually infiltrate tissues showing allergic inflammation; however, on occasion, it may participate in these inflammatory reactions.
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PMID:The neutrophil and chronic allergic inflammation. Immunochemical localization of neutrophil elastase. 217 30

Intradermal injection of allergens in sensitive subjects produces an IgE-dependent prolonged inflammatory reaction, the late phase reaction (LPR). Histologically, eosinophils are present in the LPR but are not as numerous as neutrophils or mononuclear cells. We determined whether extracellular deposition of eosinophil and neutrophil granule proteins occurs in the LPR by immunofluorescent localization of eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and neutrophil elastase. Before intradermal challenge, eosinophils and neutrophils were present only in blood vessels, and MBP, EDN, and elastase were localized to cells. At 15 minutes, small amounts of MBP, EDN and elastase were found outside of cells in focal areas. By 1 to 3 hours, MBP, EDN and elastase were extensively deposited throughout the dermis in a granular and diffuse manner; these deposits persisted up to 56 hours. Both actively and passively sensitized subjects showed similar MBP and elastase deposition. Skin sites passively sensitized by sera depleted of IgE showed essentially no MBP or elastase deposition. Electron microscopy showed degenerating eosinophils and free eosinophil granules in the dermis. Mast cell numbers diminished during the LPR when extracellular eosinophil and neutrophil granule protein deposition was maximal. These results demonstrate that striking dermal eosinophil and neutrophil granule protein deposits are prominent features of the cutaneous LPR, are IgE-dependent and precede the maximal clinical expression of the LPR. The possible significance of these findings in the pathophysiology of the LPR is discussed.
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PMID:Extracellular deposition of eosinophil and neutrophil granule proteins in the IgE-mediated cutaneous late phase reaction. 218 46

We hypothesized that repeated IgE-mediated late-phase reactions are critical in the pathogenesis of atopic dermatitis (AD). Prior studies have shown that extracellular deposition of eosinophil granule major basic protein (MBP) occurs in lesional AD skin, despite a paucity of infiltrating eosinophils, and that deposition of both neutrophil and eosinophil granule proteins occurs in the IgE-mediated late-phase reaction. We evaluated the participation of both eosinophil and neutrophil granule proteins in AD. Cutaneous biopsy specimens and serum and urine samples were obtained from 22 patients with AD. Lesional tissue was examined by means of immunofluorescence for neutrophil elastase and lactoferrin and for eosinophil granule MBP, eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP). Serum levels of elastase, MBP, EDN, and ECP and urine levels of MBP, EDN, and ECP were measured. Marked extracellular deposition of at least one of the eosinophil granule proteins was present in the dermis of 15 of the 22 AD skin specimens, but minimal or no extracellular neutrophil elastase or lactoferrin deposition was observed in any specimens. Serum and urine levels of MBP, EDN, and ECP in the patients were elevated when compared with those of normal controls, whereas serum levels of neutrophil elastase were not elevated. Serum MPB levels correlated with extent of body surface involvement. These results suggest that eosinophil degranulation occurs in AD but that neutrophil degranulation does not. Although eosinophil degranulation is prominent in both the late-phase reaction and in AD, the lack of neutrophil degranulation in AD demonstrates differences in the inflammatory reactions.
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PMID:Assessment of eosinophil and neutrophil participation in atopic dermatitis: comparison with the IgE-mediated late-phase reaction. 802 90

The late-phase allergic reaction (LPR) occurs 4 to 8 h after allergen exposure and probably causes the symptoms of chronic allergic disease. To determine the effects of soluble IL-1 receptor on the cutaneous LPR, we performed a prospective, randomized, double-blind, placebo-controlled study on 15 allergic subjects. Intradermal injections of allergen were placed on subjects' forearms, followed by immediate subcutaneous injections at the same site of either 1, 10, 25, 50, or 100 micrograms of rhu IL-1R to three subjects in each dosage group. Placebo was given to matched allergen-injected sites on the contralateral arm. Erythema, induration, and itching were recorded for each site. Sites were biopsied at 8 h for immunohistologic evaluations. Rhu IL-1R significantly reduced the clinical reaction at all concentrations. At 1 and 10 micrograms, measurements of LPR were significantly less (p < 0.05) than at placebo sites at several time points from 2 to 8 h. At higher concentrations, LPR was suppressed at rhu IL-1R and placebo sites, suggesting a systemic effect of rhu IL-1R. Histologic evaluation and indirect immunofluorescence for eosinophil granule major basic protein, neutrophil elastase, and mast cell tryptase showed no statistical differences between rhu IL-1R and placebo sites or among doses. IL-1 plays an important role in the generation of allergic LPR. While microgram quantities of rhu IL-1R inhibited the clinical signs and symptoms of LPR, its effects on the allergic inflammatory infiltrate are yet to be defined. In this short term trial, rhu IL-1R was neither immunogenic nor toxic.
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PMID:Human cutaneous allergic late-phase response is inhibited by soluble IL-1 receptor. 812 Apr 5

Urticarial dermographism and delayed pressure urticaria are two forms of physical urticaria which are well defined clinically and histologically. Previous studies have shown eosinophil granule protein deposition in urticarial reactions, including chronic urticaria, solar urticaria and delayed pressure urticaria. To evaluate and compare the involvement of granulated inflammatory cells in urticarial dermographism and delayed pressure urticaria, we studied sequential biopsies of induced lesions of urticarial dermographism and delayed pressure urticaria by indirect immunofluorescence, to detect eosinophil granule major basic protein (MBP) and neutrophil granule elastase. Biopsies from dermographic lesions at time 0, 5 min, 15 min, 2 h and 24 h, showed few infiltrating eosinophils, with minimal extracellular MBP deposition, and a few infiltrating neutrophils, with minimal neutrophil elastase deposition, throughout the evolution of the lesions. Sequential biopsies of delayed pressure urticaria at time 0, 20 min, 6, 12 and 24 h, showed eosinophil infiltration with extensive MBP deposition beginning at 20 min, and neutrophil infiltration with variable elastase deposition beginning at 20 min. Control tissue specimens from normal volunteers showed neutrophil infiltration and slight degranulation, but no eosinophil infiltration or degranulation. Comparison of urticarial dermographism with delayed pressure urticaria showed marked differences in the patterns of infiltration. Delayed pressure urticaria, with eosinophil and neutrophil degranulation, was strikingly similar to the IgE-mediated late phase reaction. In contrast, eosinophil and neutrophil involvement in urticarial dermographism was minimal. Considering the extent of eosinophil granule protein deposition and the biological activities of the eosinophil granule proteins, the findings in delayed pressure urticaria point to an important pathophysiological role of eosinophils in the disease.
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PMID:Immunohistological comparison of granulated cell proteins in induced immediate urticarial dermographism and delayed pressure urticaria lesions. 854 35

Polymorphic eruption of pregnancy (PEP) and herpes gestationis (HG) are pregnancy-related dermatoses of unknown aetiology with eosinophil infiltration which, at early stages, may show similar clinical and histopathological features. To determine the relative contributions of eosinophils, neutrophils and mast cells to the pathogenesis of PEP and HG through deposition of granule proteins, we studied tissue and serum from 15 patients with PEP and 10 with HG. Using indirect immunofluorescence with antibodies to human eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), neutrophil elastase and mast cell tryptase, we determined and compared cellular and extracellular staining patterns in lesional skin biopsy specimens and, using immunoassay, measured MBP, EDN, and ECP in patients' sera. Eosinophil infiltration and extracellular protein deposition of all three eosinophil granule proteins were present in both PEP and HG indicating a pathogenic role for eosinophils in both diseases. Staining for eosinophil granule proteins was especially prominent in urticarial lesions and around blisters in HG. EDN and ECP serum levels in PEP and ECP serum levels in HG were significantly increased compared with those in normal pregnant and normal nonpregnant serum. Neutrophils were more prominent in HG specimens than in PEP specimens; extracellular neutrophil elastase was minimally present and similar in both diseases. Mast cell numbers and extracellular tryptase deposition did not differ between the two diseases and did not differ from mast cell counts in skin of normal pregnant women. This study shows that eosinophil granule proteins are deposited extracellularly in tissue and are increased in serum in both PEP and HG. Moreover, eosinophil involvement in the two diseases is more consistent than neutrophil and mast cell involvement. Comparatively, tissue eosinophil infiltration and extracellular protein deposition is more extensive in HG than in PEP, suggesting that eosinophil involvement is greater in the pathogenesis of HG than PEP and similar to that found in bullous pemphigoid.
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PMID:Polymorphic eruption of pregnancy and herpes gestationis: comparison of granulated cell proteins in tissue and serum. 1035 84

Infection with the helminth parasite Strongyloides stercoralis (Ss) is commonly clinically asymptomatic that is often accompanied by peripheral eosinophilia. Granulocytes are activated during helminth infection and can act as immune effector cells. Plasma levels of eosinophil and neutrophil granular proteins convey an indirect measure of granulocyte degranulation and are prominently augmented in numerous helminth-infected patients. In this study, we sought to examine the levels of eosinophil, neutrophil, and mast cell activation-associated granule proteins in asymptomatic Ss infection and to understand their kinetics following anthelmintic therapy. To this end, we measured the plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, neutrophil elastase, myeloperoxidase, neutrophil proteinase-3, mast cell tryptase, leukotriene C4, and mast cell carboxypeptidase-A3 in individuals with asymptomatic Ss infection or without Ss infection [uninfected (UN)]. We also estimated the levels of all of these analytes in infected individuals following definitive treatment of Ss infection. We demonstrated that those infected individuals have significantly enhanced plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, elastase, myeloperoxidase, mast cell tryptase, leukotriene C4, and carboxypeptidase-A3 compared to UN individuals. Following the treatment of Ss infection, each of these granulocyte-associated proteins drops significantly. Our data suggest that eosinophil, neutrophil, and mast cell activation may play a role in the response to Ss infection.
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PMID:Elevated Systemic Levels of Eosinophil, Neutrophil, and Mast Cell Granular Proteins in Strongyloides Stercoralis Infection that Diminish following Treatment. 2947 56