Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating evidence supports the importance of leukocyte-endothelial cell adhesion molecule (CAM) expression as an initiating process in tissue inflammation. To investigate the relevance of CAM expression to allergic airways inflammation, nasal biopsies from patients with perennial allergic rhinitis (n = 8) and from nonatopic healthy volunteers (n = 8) were immunostained with monoclonal antibodies directed against the CAMs, intercellular adhesion molecule-1 (ICAM-1), endothelial cell adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). The endothelial staining of these CAMs was related to the number of vessels within each biopsy, delineated by a monoclonal antibody against Ulex europaeus-1 lectin bound to endothelial cells, and to the number of tissue leukocytes staining for one of the ligands of ICAM-1, the beta 2 integrin, lymphocyte function-associated antigen (LFA-1). Expression of CAMs was related to the number of infiltrating neutrophils, eosinophils, and lymphocytes identified immunohistochemically within the biopsies. ICAM-1 was the most prominent CAM present on the endothelium of the normal nasal mucosa, with less expression of ELAM-1 and only minimal or absent expression of VCAM-1. In perennial rhinitis, both ICAM-1 (P less than 0.05) and VCAM-1 (P less than 0.01) expression on endothelial cells were increased and were positively correlated in their level of expression (P less than 0.002). The number of tissue LFA-1-positive cells was significantly greater (P less than 0.05) in the biopsies from the perennial rhinitics (median, 27.3/mm2) than from the healthy controls (median, 5.3 cells/mm2). LFA-1 expression significantly correlated with the number of ICAM-1-positive vessels (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Oct
PMID:The expression of leukocyte-endothelial adhesion molecules is increased in perennial allergic rhinitis. 138 78

We examined the ability of conditioned medium (CM) generated by human upper airway epithelial (Ep) cells from normal (NN) and inflamed, allergic rhinitis (AR) and nasal polyp (NP) tissues to induce monocytic differentiation of hemopoietic progenitors of the HL-60 myeloid leukemia cell line in vitro. In HL-60 cells cultured in RPMI with 10% FBS, there was differentiation to 0.4 +/- 0.4% monocytic cells. NN-, AR-, and NP-EpCM induced differentiation to 23 +/- 6%, 42 +/- 11%, and 71 +/- 10% monocytic cells, respectively. EpCM also induced isolated peripheral blood nonadherent mononuclear cells to express monocyte/macrophage-specific antigens as detected by immunohistochemistry using FMC-32 monoclonal antibodies (anti-CD14). We also examined the cytokine content of these EpCMs and found that they contained granulocyte/macrophage colony-stimulating factor (GM-CSF): 126 +/- 35, 198 +/- 22, and 489 +/- 118 pg/ml for NN-, AR-, and NP-EpCM, respectively. These CMs also contained granulocyte-CSF (G-CSF) and interleukin-6 (IL-6), but there were no significant differences between normal and inflamed tissue-derived cell supernatants. No macrophage-CSF (M-CSF) was detected in these EpCMs. Recombinant human GM-CSF, G-CSF, and IL-6, alone and in combinations, at doses similar to or greater than those found in the EpCMs, did not induce comparable monocytic differentiation of HL-60 cells. Preincubation of the EpCM with neutralizing anti-GM-CSF, anti-G-CSF, or anti-IL-6 antibodies did not significantly inhibit the monocytic differentiation induced by the EpCM.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Mar
PMID:Monocyte-macrophage differentiation induced by human upper airway epithelial cells. 170 10

Nasal polyposis is a chronic inflammatory condition of the upper airways characterized by infiltration of activated inflammatory cells, particularly eosinophils. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a cytokine with powerful biologic effects including the regulation of survival, proliferation, and activation of granulocytes as well as differentiation of hemopoietic cells. To examine the potential role of GM-CSF in the pathogenesis of this condition, we investigated gene expression and production of GM-CSF in nasal polyp tissues as well as in the normal nasal mucosa. Immunoreactive GM-CSF was detected by enzyme-linked immunosorbent assay in the 24-h supernatant of nasal polyp tissues placed in culture. By Northern blot analysis and Southern blot analysis following a reverse-transcription polymerase chain reaction using a human GM-CSF cDNA probe, we detected GM-CSF mRNA in nasal polyp tissues, as well as in the tissue from a patient with allergic rhinitis, but not in the normal nasal mucosa. By in situ hybridization using the same probe, cells expressing mRNA specific for GM-CSF were observed in nasal polyp tissues and in the allergic nasal mucosa. In addition, by the combination of in situ hybridization and counterstaining with chromotrope 2R, we demonstrated that approximately 30% of eosinophils infiltrating the polyp tissue express the GM-CSF gene. These results suggest a novel mechanism by which eosinophils may contribute to the pathogenesis of chronic inflammatory diseases such as nasal polyposis, allergic rhinitis, and, by implication, asthma.
Am J Respir Cell Mol Biol 1991 Dec
PMID:Granulocyte/macrophage colony-stimulating factor (GM-CSF) gene expression by eosinophils in nasal polyposis. 195 76

In nasal biopsies from 17 adult patients with seasonal allergic rhinitis and from 10 healthy controls, cytokines were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR). The time-course study during winter included repeated local allergen provocation with subsequent nasal biopsies as well as biopsies taken during pollen season. The RT-PCR for CD44 yielded positive bands in 65 of 71 cases, in which cases mRNA for interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5) were thus investigated by means of seminested PCR. IL-4 mRNA was found almost exclusively in the allergic patients. During provocation a significant increase in IL-4 was noticed compared with controls (p = 0.043). Equally, during the natural pollen season, IL-4 mRNA expression was significantly higher in patients not using nasal corticosteroids compared with those who did (p = 0.011). No differences in IL-2 or IL-5 were observed between the groups. These findings also indicate, together with earlier observations of T-cell activation, a phenotype switch toward T-helper 2 (Th2) cells, and the accumulation (homing) of these T cells in the nasal mucosa, that T cells constitute the main source for IL-4 in the nasal mucosa. Therefore, allergic patients have an increased synthesis of IL-4 when provoked with the allergen, and during natural pollen season this synthesis can be downregulated by corticosteroids. Furthermore, this study exemplifies the versatility of molecular biology in surgical pathology and that even low-copy-number cytokine mRNA can be examined in routinely snap-frozen surgical specimens.
Diagn Mol Pathol 1995 Jun
PMID:Nasal messenger RNA expression of interleukins 2, 4, and 5 in patients with allergic rhinitis. 755 Dec 98

We examined the biological characteristics of normodense and hypodense eosinophils prepared from the peripheral blood of the patients with allergic rhinitis caused by house dust mites by measuring leukotriene C4 (LTC4), platelet-activating factor (PAF), and superoxide anions. The normodense (density: 1.100-1.095) and the hypodense (density: 1.080-1.070) eosinophils were prepared by a Percoll density gradient. The normodense eosinophils produced a greater amount of LTC4 (15 ng/10(6) cells) after stimulation by calcium ionophore A23187 than the hypodense eosinophils (1.8 ng/10(6) cells). On the other hand, in the hypodense eosinophils higher amounts of both PAF (5210 pg/10(7) cells/15 min) and superoxide anions (0.33 nmoles/10(7) cells/min) were produced by calcium ionophore A23187 than in the normodense eosinophils, 501 pg/10(7) cells/15 min and 0.18 nmoles/10(7) cells/min, respectively. Considering these results, it is suggested that the two eosinophil subpopulations have distinct biological roles in generating these inflammatory mediators which appear as typical pathological features of allergic rhinitis.
Biochem Mol Biol Int 1995 Aug
PMID:The pathophysiological roles of heterogeneous eosinophils in allergic rhinitis caused by house dust mites. 758 Oct

A secreted form of phospholipase A2 (PLA2) has been implicated in inflammatory disorders such as rheumatoid arthritis and sepsis. To determine if PLA2 may also play a role in allergic rhinitis, we have measured enzymic activity in nasal lavage from allergic subjects. Enhanced activity of PLA2 in the lavage was observed following nasal challenge with antigen or histamine. The PLA2 in the nasal lavage was partially purified by acid extraction, size exclusion chromatography, and ion exchange chromatography. The partially purified enzyme from nasal lavage was subsequently compared to a recombinant form of human PLA2 identified in synovial fluid from arthritic patients. The two enzymes showed similar molecular weights (15 to 16 kD) on SDS-PAGE, and both reacted with a rabbit polyclonal antiserum raised to a galactokinase-PLA2 fusion protein. The enzymatic activities of the two PLA2s were indistinguishable when compared for ionic dependence, substrate selectivity, and sensitivity to inhibitors. These results suggest that the PLA2 induced in nasal lavage in response to challenge by antigen is very similar to the extracellular PLA2 found in synovial fluid from subjects with rheumatoid arthritis and may play a role in the inflammatory processes associated with allergic rhinitis.
Am J Respir Cell Mol Biol 1994 Jul
PMID:Characterization of phospholipase A2 from human nasal lavage. 801 33

We have investigated the phenotype of interleukin-5 (IL-5) mRNA+ cells in the nasal mucosa of subjects with allergic rhinitis. Serial cryostat sections were cut from paraformaldehyde-fixed snap-frozen nasal biopsies from six patients, before and 24 h after local allergen provocation with grass pollen. Immunocytochemistry (APAAP) was followed by in situ hybridization on the same sections. For immunocytochemistry, antibodies against CD3, tryptase, and major basic protein (MBP) were used to identify T cells, mast cells, and eosinophils, respectively. Hybridization studies were performed using a Digoxigenin-labeled IL-5 riboprobe. Nitroblue tetrazolium (NBT) and X-phosphate-5-bromo-4-chloro-3- indoly phosphate (BCIP) served as chromogens to detect hybridized IL-5 mRNA signals. The majority of IL-5 mRNA+ cells were CD3+ (83.2%), whereas the remainder were either tryptase+ (11.3%) or MBP+ (5.4%). In contrast, only a few IL-5 mRNA+ cells were observed in nasal biopsies before challenge, all of which were co-localized to CD3+ cells. These results indicate that CD3+ cells are the principal cellular source of IL-5 transcripts in the nasal mucosa 24 h after allergen-induced late-phase nasal responses.
Am J Respir Cell Mol Biol 1993 Oct
PMID:T cells are the principal source of interleukin-5 mRNA in allergen-induced rhinitis. 839 74

The allergen-induced late nasal response (LNR) is associated with high expression of interleukin-4 (IL-4) and IL-5 messenger RNA (mRNA) in the nasal mucosa, suggesting a role for Th2-type cytokines in the development of the LNR. Moreover, topical corticosteroid-mediated inhibition of the LNR is accompanied by inhibition of IL-4, but not IL-5, mRNA expression, IL-13 shares a number of functions with IL-4, including IgE switching and vascular cell adhesion molecule-1 (VCAM-1) upregulation. We investigated the expression of IL-13 mRNA and immunoreactivity in nasal biopsies from 10 normal subjects and 20 subjects with allergic rhinitis. IL-4 mRNA expression was examined in the same subjects. The allergic rhinitis patients were randomized to receive a 6-wk treatment with either topical fluticasone propionate (n = 10) or placebo (n = 10) nasal spray twice daily. A nasal biopsy was taken before treatment and 24 h after local nasal allergen provocation with a grass-pollen extract. Before treatment, there was no significant difference between the allergic rhinitis patients and controls in the expression of IL-13 mRNA and immunoreactivity. After allergen provocation, we observed a significant increase in IL-13 mRNA-positive and immunoreactive cells at 24 h only in subjects given placebo (P < 0.001). Inhibition of the LNR after corticosteroid treatment was associated with a marked decrease in allergen-induced IL-13 mRNA-positive (P < 0.001) and immunoreactive cells (P < 0.001). In subjects given placebo, 76.9 +/- 5.5% of IL-13 mRNA-positive cells observed after allergen were CD3+, whereas 11.2 +/- 2.7% coexpressed immunoreactivity for mast-cell tryptase. In these subjects, increases in cells expressing IL-13 mRNA were greater than for IL-4 mRNA (P = 0.001), and double in situ hybridization studies revealed that 100% of the IL-4 mRNA-positive cells coexpressed IL-13 mRNA, whereas 66.6 +/- 10.5% of IL-13 mRNA-positive cells coexpressed IL-4 transcripts after allergen challenge. The results of this study suggest that IL-13 expression is a prominent feature of the LNR, and that inhibition of the LNR following steroid therapy may be partly attributable to inhibition of IL-13 expression.
Am J Respir Cell Mol Biol 1997 Jul
PMID:IL-13 mRNA and immunoreactivity in allergen-induced rhinitis: comparison with IL-4 expression and modulation by topical glucocorticoid therapy. 922 5

Eotaxin is an eosinophil-specific chemokine associated with the recruitment of eosinophils to the site of allergic inflammation. The aims of this study were to determine the expression of eotaxin in nasal biopsies from allergic and nonallergic individuals with chronic severe sinusitis, and to examine whether the expression of this chemokine is upregulated following allergen challenge in the nasal mucosa of patients with allergic rhinitis. We also undertook to phenotype of inflammatory cells within the submucosa expressing eotaxin mRNA. Nasal turbinate tissue from 16 individuals with allergic or nonallergic chronic sinusitis and 10 normal controls were examined for the presence of eotaxin mRNA and immunoreactivity by in situ hybridization and immunocytochemistry. The numbers of cells expressing eotaxin mRNA were also determined after either allergen or diluent challenge in atopic subjects with a history of allergic rhinitis. There was a constitutive expression of eotaxin-immunoreactivity and the presence of eotaxin mRNA-positive cells in nasal biopsies from normal individuals. Compared with normal controls, the numbers of cells expressing eotaxin mRNA and protein were significantly increased in both allergic and nonallergic sinusitis (P < 0.001). Eotaxin mRNA was expressed by nasal epithelial cells and primarily colocalized to CD68-positive macrophages within the subepithelium. In subjects with allergic rhinitis, allergen challenge markedly increased the numbers of cells expressing eotaxin mRNA and immunoreactivity in the epithelial and subepithelial cell layers (P < 0.05). This could be largely attributed to a local increase in eotaxin production within the nasal tissues. The results of this study demonstrate the constitutive expression of eotaxin and show that the numbers of cells expressing eotaxin mRNA are increased within the epithelial and subepithelial layers of the nasal mucosa in individuals with chronic sinusitis. Furthermore, allergen challenge of the nasal mucosa in atopic subjects results in a local upregulation of eotaxin expression. These data suggest a potential role for this chemokine in the pathogenesis of allergic and nonallergic eosinophilic inflammation characterizing chronic sinusitis and allergic rhinitis.
Am J Respir Cell Mol Biol 1997 Dec
PMID:Eotaxin mRNA and protein expression in chronic sinusitis and allergen-induced nasal responses in seasonal allergic rhinitis. 940 55

Ragweed (Ambrosia artemisiifolia) is clinically the most important source of seasonal aeroallergens, as it is responsible for the majority and most severe cases of hay fever (allergic rhinitis). Extracts from pollen grains have been shown to contain numerous proteins with various functions, including a novel serine proteolytic enzyme with chymotrypsin-like specificity that has been previously described (J. Biol. Chem. 1996; 271:26227-26232). We now report the isolation and properties of a second, trypsin-like enzyme with a molecular mass near 80 kD, from ragweed pollen extracts. This enzyme has a blocked N-terminus, a pH optimum near 9.0, and requires Ca2+ for stability and activity, but not reducing agents. The enzyme is inhibited by diisopropyl fluorophosphate, a general serine class proteinase inhibitor, and more specifically by N-p-tosyl-L-lysine chloromethyl ketone. Activity toward protein substrates was not detected, but various synthetic substrates and small biologically active peptides were efficiently cleaved, with a strong preference for Arg in the P1 position and either Arg or Gly in the P2 position. This specificity was confirmed through inhibition studies with both peptidyl chloromethyl ketone and organophosphate inhibitors. Significantly, atrial natriuretic peptide and angiotensin 2, whose degradation would amplify kinin activity and influence inflammatory diseases of the respiratory tract and nasal passages, were also rapidly hydrolyzed. Thus, the ragweed pollen endopeptidase may be involved in the inactivation of regulatory neuropeptides during pollen-initiated allergic reactions.
Am J Respir Cell Mol Biol 1998 Mar
PMID:Purification and characterization of an arginine-specific peptidase from ragweed (Ambrosia artemisiifolia) pollen. 949 Jun 54


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