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Z Marom

Publications and source records attributed to Z Marom.

At least 37 records · Page 2Linked to original sources
PubMed1991

Evidence for accessory cell function by class II MHC antigen-expressing airway epithelial cells.

Expression of major histocompatibility complex (MHC) class II antigens is a requirement for accessory cell function in antigen presentation. Recent reports have demonstrated the presence of class II antigens on human bronchial epithelial cells. In the present study, immunohistochemical staining revealed HLA-DR on human airway epithelial cells obtained from two different mucosal sites (lobar bronchus and nasal turbinates). To determine whether airway epithelial cells bear functional class II molecules that allow for their cognate interaction with T lymphocytes, cells isolated from these sites were used in mixed lymphocyte cultures (MLR), as an in vitro model of accessory cell function. Freshly isolated cells (11 bronchi/3 turbinates) stimulated allogeneic T lymphocytes (stimulation index [S.I.] = 9.3 [mean]; P less than 0.001 compared to T cells alone). In order to assess the potential role of contaminating conventional accessory cells, bronchial epithelial cell isolates were first preincubated in a serum-free, growth factor-supplemented medium that functionally eliminates potential non-epithelial stimulators prior to MLR culture. Conventional accessory cell-depleted epithelial cells were still capable of stimulating allogenic T lymphocytes in 18 of 23 MLR cultures (S.I. = 5.5 [mean]; P less than 0.0005 compared to T cells alone). The addition of an anti-class II monoclonal antibody (VG2.2) at the onset of culture completely inhibited the MLR response (n = 10). No shift in the CD4+/CD8+ ratio was detected between lymphocytes harvested from airway epithelial cell MLR (1.42 +/- 1.29) and the ratio from T lymphocytes cultured alone (1.3 +/- 0.75), suggesting that both CD4+ and CD8+ T lymphocytes were proliferating in response to stimulation from alloepitopes recognized on airway epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1990

Erythromycin inhibits respiratory glycoconjugate secretion from human airways in vitro.

Erythromycin and other antibiotics have been used empirically in the treatment of patients with chronic obstructive pulmonary disease (COPD). We studied whether this empirical role of antibiotics might not be related to a possible direct effect on respiratory glycoconjugate (RGC) secretion. The effect of erythromycin on RGC secretion and hypersecretion was studied in an in vitro preparation of human airways that were secreting [3H]glucosamine respiratory glycoconjugate (RGC), and on a human endometrial adenocarcinoma cell line secreting a glycoconjugate (tumor glycoconjugate = TGC) chemically similar to the RGC secreted by the airways. Erythromycin at 10(-5) M reduced RGC secretion by 35 +/- 4% (n = 9, p less than 0.001) in both human airways and the adenocarcinoma cells, and was increasingly active in the pharmacologic range of 10(-7) to 10(-4) M. The inhibitory effect of erythromycin was maximal within 16 h and was still evident 34 h after incubation. Erythromycin was noted to reduce both spontaneous (baseline) and stimulated RGC secretion (by histamine and methacholine) from airways in culture. The blocking effect appeared to be more selective for histamine than methacholine. These effects were not associated with any toxicity to the tissues and were not associated with the inhibition of protein synthesis. Dexamethasone also inhibited RGC release in both assay systems and exhibited dose-related effects in the physiologic ranges (10(-9) to 10(-5) M). When administered together, erythromycin and dexamethasone had an additive inhibitory effect on RGC secretion (68.0 +/- 3.0%, n = 7, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1990

Macrophage (monocyte)-derived mucous secretagougue (MMS) is released into the fluid of the middle ear of patients with otitis media with effusion.

Macrophage (monocyte)-derived secretagogue (MMS) is a low molecular weight peptide released by activated macrophages. This substance can enhance incorporation of carbohydrates into protein and result in the production of glycoproteins. It is believed that increased glycoproteins lead to the increased tenaciousness of mucoid effusions. Sixteen of 28 middle ear effusions demonstrated significant amounts of MMS. It is suggested that MMS is produced by activated macrophages in MEE and may lead to the development of glycoprotein by secretory epithelial cells. This substance may lead to the development of the mucoid effusion in otitis media with effusion in children.

Adolescent↗
PubMed1989

The effect of cotton bract extract on respiratory glycoconjugate secretion from human airways in vitro.

In vivo and in vitro studies with a water-soluble extract of cotton bracts (CBE) suggest that CBE may be responsible for some of the clinical manifestations of byssinosis. Since chronic bronchitis has been repeatedly documented as a major feature of byssinosis, we studied the effect of CBE on respiratory glycoconjugate (RGC) release from human airways (HAs) in vitro. HAs were incubated with [3H]glucosamine to label RGC molecules. CBE in increasing concentrations was added to radiolabeled HAs, and the release of 3H-RGC, histamine, and other mediators was measured. CBE in concentrations of 1 to 7 mg/ml caused a dose-related increase in RGC, as well as histamine release (RGC, 14% to 45% increase above control; histamine, 12 to 70 ng/ml released concurrently). Additionally, CBE in a dose of 5 mg/ml caused a more than threefold increase in peptidoleukotriene production above baseline. The effect of histamine H1 and H2 (pyrilamine and cimetidine), cyclooxygenase pathway inhibitor (indomethacin), leukotriene (LY 171883 and FPL 55712), and lipoxygenase pathway (BW nordihydroguaiarectic acid) blocking agents on CBE-induced RCG secretion was studied. In addition to histamine-H1 blockers, lipoxygenase inhibitors (nordihydroguaiarectic acid and BW 755C) and leukotriene blockers (FPL 55712 and LY 171883) are also potent inhibitors of CBE-induced RGC secretion. This suggests that CBE may act via the release of several mediators (histamine and leukotrienes), possibly from airway cells, such as mast cells, macrophages, or epithelial cells, to stimulate RGC secretion.

Bronchi↗
PubMed1989

Chronically obstructed sinonasal secretions: observations on T1 and T2 shortening.

Clinically assessed chronic proteinacious sinonasal secretions usually have long T1 and T2 relaxation times reflecting their high water content. However, in some cases variable combinations of short and long T1 and T2 relaxation times are found. To study the causes of these findings, the magnetic resonance (MR) images of 41 patients with surgically proved, chronically obstructed sinonasal secretions were studied. The relative signal intensities on both T1- and T2-weighted sequences of the sinus specimens were correlated with the gross viscosity of the specimens at surgery. Ten specimens were collected that were not contaminated with either blood or saline. UV spectrophotometric analysis of four of these samples excluded the presence of methemoglobin. Total protein content was determined in five samples, and in vitro T1 and T2 values were measured in one sample. These T1 and T2 relaxation times were accurately predicted with use of a standard pure lysozyme protein solution with the same concentration as the specimen. In addition, the observed T1- and T2-weighted signal intensities on the 41 MR images were predicted from an analysis of pure protein solutions. This study concludes that the primary causes of the variable T1 and T2 relaxation times of chronic sinonasal secretions are the macromolecular protein concentration, the amount of free water, and the specimen viscosity. Furthermore, an orderly and predictable transition of these signal intensities occurs over time.

Chronic Disease↗
PubMed1988

Dexamethasone inhibits respiratory glycoconjugate secretion from feline airways in vitro by the induction of lipocortin (lipomodulin) synthesis.

The effect of glucocorticoids on respiratory glycoconjugate (RGC) secretion was studied in a cat tracheal organ culture system. Dexamethasone (10(-5) to 10(-9) M) added to culture medium for 24 h caused a dose-related reversible inhibition of RCG of as much as 40% with a peak effect at 24 to 60 h after initiation of dexamethasone treatment. A monoclonal antilipocortin antibody added to the cultures blocked the inhibitory effect of dexamethasone on RGC secretion and accelerated the reversal of the dexamethasone effect after discontinuation of dexamethasone treatment. A control antibody without antilipocortin activity had no effect on RGC secretion or dexamethasone-induced inhibition of RGC secretion. Measurement of the concentration of lipocortin in airways revealed a 220% increase after treatment with dexamethasone for 24 h. We conclude that dexamethasone inhibits RGC secretion through the induction of lipocortin synthesis.

Animals↗
PubMed1986

Human respiratory mucus.

Respiratory mucous glycoproteins may serve a number of protective functions for the airways; however, excessive secretions contribute to the morbidity of a variety of diseases including asthma, chronic bronchitis, and cystic fibrosis. Respiratory secretions are a mixture of cells, fluid, transudated and locally produced proteins, and mucous glycoproteins. The mucous glycoproteins give these secretions their characteristic viscosity and elasticity. While the physiologic control of mucous glycoprotein secretion is not completely understood, cholinergic, alpha-adrenergic, and beta-adrenergic stimuli may all contribute. Respiratory mucus hypersecretion seen in immediate hypersensitivity or inflammatory states may be due to reflex hypersecretion, to a variety of mediators (including histamine and cyclooxygenase or lipoxygenase pathway metabolites of arachidonic acid), or to substances released from phagocytic cells (such as macrophages, monocytes, or neutrophils). The limited number of specific approaches currently available for treating respiratory mucus hypersecretion include therapy of any underlying or intercurrent disease, improving clearance of secretions, and reducing mucus secretion with the use of glucocorticosteroids or anticholinergic drugs.

Animals↗
PubMed1985

Anaphylatoxin C3a enhances mucous glycoprotein release from human airways in vitro.

Because C3a may be generated during the course of pulmonary inflammatory reactions, we investigated the ability of C3a to affect mucous glycoprotein (MGP) secretion from cultured human airways. C3a, but not C3a des Arg, caused a dose-related increase in MGP release (maximal after 4-6 h), with as little as 15 micrograms of C3a per milliliter stimulating a 40% increase. The experimental evidence suggested that immunologically specific C3a was required for the secretagogue actions, as monospecific anti-C3a inhibited the reaction, as well as specifically absorbing the secretagogue from solution. Moreover, it appeared that C3a does not require mast cell activation, eicosanoid generation, or macrophage-derived mucus secretagogue synthesis for its effect, since (a) no evidence of histamine release accompanied C3a-induced MGP release, and dibutyryl cAMP failed to affect C3a-induced MGP release, while reducing the actions of reversed anaphylaxis; (b) MGP release caused by C3a was not influenced by eicosatetraynoic acid or specific cyclooxygenase inhibitors, and no leukotrienes were detectable on the supernatants of C3a-stimulated airways; and (c) cycloheximide failed to affect C3a secretion-stimulating actions. Thus, C3a is a potent mucus secretagogue, and, possibly, acts directly as a glandular stimulant. It seems likely that C3a generated in the course of pulmonary inflammation might contribute to the mucus secretion associated with pulmonary infections.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1985

Human monocyte-derived mucus secretagogue.

Human peripheral monocytes were stimulated with opsonized zymosan or protein A-containing Staphylococcus aureus to examine whether factors might be released that were capable of stimulating mucous glycoprotein release from cultured human airways, as has recently been described with human pulmonary macrophages. While the supernatant from monocytes exposed to opsonized zymosan or protein A-containing S. aureus caused an impressive activity was found in the control samples that were cultured in parallel and exposed to nonactivated zymosan or S. aureus that was deficient in protein A. The responsible factor was termed monocyte-derived mucus secretagogue (MMS). The maximum MMS release was reached 4-8 h after stimulation, and the amount of MMS released was dependent on the dose of opsonized zymosan added. Chromatographic analyses of MMS indicate that its molecular weight was approximately 2,000 and that the isoelectric point (pI) was 5.2, with a smaller second peak of 7.4 on isoelectric focusing. MMS itself was not detected in monocyte lysates, nor was it formed by monocytes treated with the protein synthesis inhibitor, cycloheximide, before exposure to activating particles. MMS was not a prostaglandin, could not be extracted into organic solvents, and is probably not an eicosanoid. Based on these observations, we conclude that stimulated human peripheral monocytes synthesize a small, acidic molecule, termed MMS, that is capable of stimulating human airways to secrete mucus and in nearly every respect is identical to pulmonary macrophage-derived MMS.

Chromatography↗
PubMed1984

Human pulmonary macrophage-derived mucus secretagogue.

Human pulmonary macrophages (PM) obtained from surgically removed human lung tissue released a factor after exposure to activated zymosan that caused cultured human airways to release increased amounts of radiolabeled mucous glycoproteins. The factor was released maximally after 4-8 h of zymosan exposure and caused a dose-related increase in glycoprotein release; it was termed macrophage-derived mucus secretagogue (MMS). MMS release was produced in a dose-dependent fashion by activated but not by nonactivated zymosan. The activation of zymosan was C3 dependent, and C3b-coated Sepharose was also an effective stimulant. The data suggested that cell surface activation of the PM was a sufficient stimulus to cause MMS release and that both C3-dependent activation as well as Fc receptor activation were effective. The synthesis of MMS was sensitive to cycloheximide, and no active MMS was detectable intracellularly. To determine if MMS might be one of the oxidative derivatives of arachidonic acid, PM were incubated with cyclooxygenase and lipoxygenase inhibitors before activation. These maneuvers did not influence MMS generation. MMS-rich supernatants were then extracted into organic solvents or exposed to lipophilic resin; in both cases, MMS remained in the aqueous phase. Thus, MMS is not a derivative of arachidonic acid. Sequential fractionation of MMS on ultramembrane and gel filtration followed by isoelectric focusing and gel filtration indicated that MMS is a small (approximately 2000 daltons), acidic (pI, 5.15) molecule. Therefore, surface activation of human PM results in the synthesis and release of a small acidic molecule that causes airway mucous glands to secrete increased quantities of mucous glycoproteins.

Animals↗
PubMed1984

Prostaglandin-generating factor of anaphylaxis induces mucous glycoprotein release and the formation of lipoxygenase products of arachidonate from human airways.

The effects of prostaglandin-generating factor of anaphylaxis (PGF-A) upon the lipoxygenation of arachidonic acid and the promotion of mucous glycoprotein secretion by human airways were analyzed concurrently in order to determine the role that lipoxygenase products play in the secretion of mucus which accompanies immediate hypersensitivity reactions of airways. PGF-A enhanced both mucous glycoprotein release and the 5- and 15-lipoxygenation of arachidonic acid as well as the formation of leukotriene B4 (LTB4) with similar dose-response relationships. The capacity of PGF-A to stimulate mucous glycoprotein release was inhibited by ETYA but not by indomethacin, suggesting that PGF-A stimulated lipoxygenase products may be involved. Lipoxygenase products of arachidonic acid thus may serve as mediators of the enhancement of mucus secretion from human airways in response to PGF-A.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1984

The effects of corticosteroids on mucous glycoprotein secretion from human airways in vitro.

In order to examine the mechanisms by which corticosteroids may benefit some patients with bronchorrhea, cultured human airways releasing [3H]glucosamine labeled mucous glycoproteins were exposed to corticosteroids, and mucus release was examined. Both dexamethasone and methylprednisolone produced dose-related suppression of the spontaneous release of radiolabeled mucous glycoproteins. The inhibitory effects of dexamethasone were maximal after 18 to 24 h and returned to control levels by 34 h. In order to study the effects of dexamethasone on stimulated mucus release, airways were exposed to dexamethasone and to the mucus secretagogues, histamine or 5-monohydroxyeicosatetraenoic acid. Both of these secretagogues stimulated radiolabeled mucous glycoprotein release from airways that had never been exposed to corticosteroids, as well as in a reduced fashion from corticosteroid-treated airways. The reduced mucus release caused by secretagogues from dexamethasone-treated airways appeared to reflect a lowered baseline secretion rate rather than a specific inhibition of either secretagogue.

Arachidonic Acids↗
PubMed1984

Production of mucous glycoproteins by nasal turbinates in vitro.

An in vitro system of human nasal turbinate tissue culture has been developed. Nasal turbinate tissue resected during surgery for nasal obstruction is dissected free of bone, placed on absorbable gelatin sponges, and cultured with CMRL-1066 medium containing antibiotics. Viability of explants may be demonstrated both physiologically and histologically through a period of 4 weeks. 3H-glucosamine added to the medium is biosynthetically incorporated into mucous glycoprotein (MGP). Gel filtration column chromatography on Sephacryl S-1000 in 6M urea in 0.005M phosphate buffer demonstrates human turbinate MGP to fractionate with 85% of the radiolabel filtered and 15% excluded by the column. The excluded MGP fractionates with globular proteins of greater than 20 X 10(6) daltons, while the fractions that enter the column filter with molecular sizes of 0.4 X 10(6) to 20 X 10(6) daltons. MGP synthesized by human lung airways has comparable sizing characteristics, suggesting a similarity in upper and lower airway mucus chemistry.

Culture Techniques↗
PubMed1984

Human respiratory mucous glycoproteins.

Biochemical characterization of human respiratory mucus has generally utilized expectorated specimens. In order to exclude extraneous contaminants in the analysis of airway glycoproteins, human airways were cultured and the mucous glycoprotein released into the supernatant analyzed. By incorporating 3H-labeled glucosamine or 14C-threonine into the media, the airways biosynthetically labeled the mucous glycoproteins (MGP), facilitating their analysis. The MGP chromatograph by gel filtration on Sepharose 2B in two fractions: one excluded from the column and one that enters the column. However, employing a gel filtration column with the ability to fractionate larger molecules, Sephacryl S-1000, it was found that MGP fractionate over a large range in molecular sizes and do not segregate into distinct fractions. The diffuse, broad peak of MGP fractionation on Sephacryl S-1000 is not affected by reduction and alkylation or by chromatography in 1 M NaCl. The fractionated MGP from Sepharose 2B were divided into larger and smaller molecular species, and their charge characteristics were determined by DEAE chromatography and preparative isoelectric focussing. MGP exhibit strong acidic charge characteristics that are uniform, as reflected in elution from DEAE and a single, sharp isoelectric focussing point. Enzymatic cleavage of the oligosaccharide side chains from MGP liberates more than 70% of the radiolabeled side chains. The side chains enzymatically cleaved from the larger and smaller molecular species of MGP are similar in size. Highly purified MGP were found to be 73% carbohydrate and 27% protein. Thus, human airways release a family of MGP that express marked heterogeneity in size but a uniform, strong acid charge and include side chains of similar size.

Carbohydrate Metabolism↗