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Biomedical subjects

M M Glovsky

Publications and source records attributed to M M Glovsky.

At least 19 recordsLinked to original sources
PubMed2004

Birch pollen rupture and the release of aerosols of respirable allergens.

BACKGROUND: Birch pollen allergens have been implicated as asthma triggers; however, pollen grains are too large to reach the lower airways where asthmatic reactions occur. Respirable-sized particles containing birch pollen allergens have been detected in air filters, especially after rainfall but the source of these particles has remained speculative. OBJECTIVE: To determine the processes by which birch pollen allergens become airborne particles of respirable size with the potential to contribute to airways inflammation. METHODS: Branches with attached male catkins were harvested and placed in a controlled emission chamber. Filtered dry air was passed through the chamber until the anthers opened, then they were humidified for 5 h and air-dried again. Flowers were disturbed by wind generated from a small electric fan. Released particles were counted, measured and collected for immuno-labelling and high-resolution microscopy. RESULTS: Birch pollen remains on the dehisced anther and can rupture in high humidity and moisture. Fresh pollen takes as long as 3 h to rupture in water. Drying winds released an aerosol of particles from catkins. These were fragments of pollen cytoplasm that ranged in size from 30 nm to 4 microm and contained Bet v 1 allergens. CONCLUSION: When highly allergenic birch trees are flowering and exposed to moisture followed by drying winds they can produce particulate aerosols containing pollen allergens. These particles are small enough to deposit in the peripheral airways and have the potential to induce an inflammatory response.

Allergens↗
PubMed2001

Complement-dependent immune complex-induced bronchial inflammation and hyperreactivity.

Bronchoconstriction responses in the airway are caused by multiple insults and are the hallmark symptom in asthma. In an acute lung injury model in mice, IgG immune complex deposition elicited severe airway hyperreactivity that peaked by 1 h, was maintained at 4 h, and was resolved by 24 h. The depletion of complement with cobra venom factor (CVF) markedly reduced the hyperreactive airway responses, suggesting that complement played an important role in the response. Blockade of C5a with specific antisera also significantly reduced airway hyperreactivity in this acute lung model. Complement depletion by CVF treatment significantly reduced tumor necrosis factor and histamine levels in bronchoalveolar lavage fluids, correlating with reductions in airway hyperreactivity. To further examine the role of specific complement requirement, we initiated the immune complex response in C5-sufficient and C5-deficient congenic animals. The airway hyperreactivity response was partially reduced in the C5-deficient mice. Complement depletion with CVF attenuated airway hyperreactivity in the C5-sufficient mice but had a lesser effect on the airway hyperreactive response and histamine release in bronchoalveolar lavage fluids in C5-deficient mice. These data indicate that acute lung injury in mice after deposition of IgG immune complexes induced airway hyperreactivity that is C5 and C5a dependent.

Animals↗
PubMed1998

Upper airways involvement in bronchial asthma.

The upper airways--the nose, pharynx, and mouth--lead through the larynx and into the tracheobronchial tree of the lung (the lower airways). This cavernous void in the upper airways transports external air to the alveolar sacs, in the distal segments of the tracheobronchial tree. Oxygen is absorbed from the alveolar sacs and carbon dioxide is released. Yet, under adverse physiologic conditions such as allergic or nonallergic rhinitis, sinusitis, and bronchitis, obstruction of the upper and lower airways occurs and leads to sneezing, rhinitis, and bronchospasm. The simultaneous occurrence of upper airways disease and asthma is addressed in this review.

Asthma↗
PubMed1996

Comparative effect of C3a and C5a on adhesion molecule expression on neutrophils and endothelial cells.

Complement activation is known to enhance neutrophil binding to human umbilical vein endothelial cells (HUVECs). Recently, we have shown that recombinant human C5a upregulates P-selectin in HUVECs. Unstimulated human neutrophil binding is also increased on C5a stimulated HUVECs. We demonstrate in this report that C5a upregulates CD11b/CD18 in human neutrophils. Also shown is that synthetic C3a57-77 and an analog 15 amino acid C3a peptide (C3a15) neither upregulate CD11b/CD18 nor do the C3a peptides increase P-selectin, ICAM-1 or E-selectin in HUVECs. Thus C5a and not C3a is responsible for early (approximately 30 minutes) neutrophil adhesion to endothelial cells after complement activation.

Amino Acid Sequence↗
PubMed1996

Latex allergens in tire dust and airborne particles.

The prevalence and severity of latex allergy has increased dramatically in the last 15 years due to exposure to natural rubber products. Although historically this health risk has been elevated in hospital personnel and patients, a recent survey has indicated a significant potential risk for the general population. To obtain a wide-spread source for latex exposure, we have considered tire debris. We have searched for the presence of latex allergens in passenger car and truck tire tread, in debris deposited from the atmosphere near a freeway, and in airborne particulate matter samples representative of the entire year 1993 at two sites in the Los Angeles basin (California). After extraction of the samples with phosphate buffered saline, a modified-ELISA inhibition assay was used to measure relative allergen potency and Western blot analyses were used to identify latex allergens. The inhibition studies with the human IgE latex assay revealed inhibition by the tire tread source samples and ambient freeway dust, as well as by control latex sap and latex glove extracts. Levels of extractable latex allergen per unit of protein extracted were about two orders of magnitude lower for tire tread as compared to latex gloves. Western blot analyses using binding of human IgE from latex-sensitive patients showed a band at 34-36 kDa in all tire and ambient samples. Long Beach and Los Angeles, California, air samples showed four additional bands between 50 and 135 kDa. Alternative Western blot analyses using rabbit IgG raised against latex proteins showed a broad band at 30-50 kDa in all samples, with additional bands in the urban air samples similar to the IgE results. A latex cross-reactive material was identified in mountain cedar. In conclusion, the latex allergens or latex cross-reactive material present in sedimented and airborne particulate material, derived from tire debris, and generated by heavy urban vehicle traffic could be important factors in producing latex allergy and asthma symptoms associated with air pollution particles.

Air Pollutants↗
PubMed1995

Cetirizine in patients with seasonal rhinitis and concomitant asthma: prospective, randomized, placebo-controlled trial.

OBJECTIVE: This study explored the safety and efficacy of cetirizine for treatment of allergic rhinitis and asthma. METHODS: Daily treatment for 6 weeks with cetirizine 10 mg (93 patients) was compared with placebo treatment (93 patients) in a randomized, double-blind parallel study of patients with allergic rhinitis and asthma. This multicenter study was started just before onset of the fall pollen season. Rhinitis and asthma symptoms were assessed twice daily; spirometry was performed weekly. RESULTS: Placebo-treated patients experienced a worsening of rhinitis symptoms from baseline throughout the study, whereas cetirizine-treated patients had a significant improvement in rhinitis symptoms at week 1, which was maintained after onset of the pollen season. Asthma symptoms in the cetirizine group improved from baseline at week 1; symptoms were significantly better than in the placebo group for 5 of 6 weeks of the study. Pulmonary function did not worsen in patients taking cetirizine or placebo; there were no differences between treatments as determined by spirometry. Albuterol use was less frequent in the cetirizine-treated patients for every week of the study, but differences did not reach significance. Pseudoephedrine use was similar in both groups. More cetirizine-treated patients (90%) completed the trial than did placebo-treated patients (74%). Both treatments were well tolerated. CONCLUSION: Cetirizine 10 mg daily is safe and effective in relieving both upper and lower respiratory tract symptoms in patients with seasonal allergic rhinitis and concomitant asthma.

Adolescent↗
PubMed1994

C5a-induced expression of P-selectin in endothelial cells.

Human umbilical vein endothelial cells have recently been shown to respond to C5a with increases in intracellular Ca2+, production of D-myo-inositol 1,4,5-triphosphate and superoxide anion generation. In the current studies, C5a had been found to cause in a time- and dose-dependent manner rapid expression of endothelial P-selectin, secretion of von Willebrand factor, and adhesiveness for human neutrophils. The effects of C5a in P-selectin expression and adhesiveness of neutrophils were similar to the effects of histamine and thrombin on endothelial cells. The adhesiveness of C5a-stimulated endothelium for neutrophils was blocked by anti-P-selectin, but not by antibodies to intercellular adhesion molecule 1, E-selectin, or CD18. A cell-based ELISA technique has confirmed upregulation of P-selectin in endothelial cells exposed to C5a. Binding of C5a to endothelial cells has been demonstrated, with molecules bound being approximately 10% of those binding to neutrophils. By a reverse transcriptase-PCR technique, endothelial cells have been shown to contain mRNA for the C5a receptor. These data suggest that C5a may be an important inflammatory mediator for the early adhesive interactions between neutrophils and endothelial cells in the acute inflammatory response.

Cell Adhesion↗
PubMed1992

Effect of adenylate cyclase activators on C5a-induced human neutrophil aggregation, enzyme release and superoxide production.

The effect of adenylate cyclase activators on C5a- and f-Met-Leu-Phe-induced human neutrophil aggregation, enzyme release and superoxide production was investigated. C5a-stimulated superoxide production was markedly inhibited by adenylate cyclase activators, and the order of potency was PGE1 greater than isoproterenol greater than epinephrine greater than PGF2 alpha, which correlated with intracellular cAMP levels. However, neutrophil aggregation was inhibited by PGE1, PGE2, isoproterenol and epinephrine only at concentrations greater than 10(-6) M. Lysozyme release was inhibited only via PGEs in the presence of the phosphodiesterase inhibitor, methylisobutylxanthine. These results suggest that in the human neutrophil: (1) C5a-induced superoxide production is more sensitive to regulation by cAMP than neutrophil aggregation or enzyme release, and (2) the type of receptor occupied as well as the threshold level of cAMP are important in the regulation of neutrophil aggregation and enzyme release stimulated by C5a.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Proteins of the complement system and acute phase reactants in sera of patients with spinal cord injury.

Complement activity was studied in patients with spinal cord transection. In some sera acute phase reactants: haptoglobin, C-reactive proteins, ceruloplasmin, as well as fibrinogen and fibrin degradation products, and immune complexes were monitored. Complement and acute phase reactants are increased in a majority of patients. Continuing inflammation and release of inflammatory mediators could be responsible for poor healing that commonly occurs in spinal cord injury. Urinary tract and other infections are associated with some but not all of the protein abnormalities. These proinflammatory proteins may contribute to the lack of healing of spinal transection.

Acute-Phase Proteins↗
PubMed1991

Effect of maternal immunotherapy on immediate skin test reactivity, specific rye I IgG and IgE antibody, and total IgE of the children.

The effect of specific immunotherapy during pregnancy was studied in 14 children, 3 to 12 years after delivery. Fourteen additional children from the same allergic mothers, in whom immunotherapy was not given during the pregnancy, served as controls. The immediate skin test response to grass allergens of the children of mothers given immunotherapy. Levels of rye I IgG and total IgE were lower in the sera of children born to mothers who received immunotherapy (not statistically significant) than their control cohorts. Paired cord blood and maternal blood samples drawn at delivery showed similar levels of rye I IgG, indicating that blocking antibody freely crosses the placenta. This evidence indicates that immunotherapy during pregnancy may have an inhibitory effect on immediate skin reactivity to grass allergens in some of the offspring. Whether tolerance to other allergens can be induced in children by maternal immunotherapy remains to be determined.

Adolescent↗
PubMed1990

C3a57-77, a C-terminal peptide, causes thromboxane-dependent pulmonary vascular constriction in isolated perfused rat lungs.

Pulmonary hypertension occurs after the intravascular activation of complement. However, it is unclear which activated complement fragments are responsible for the pulmonary vascular constriction. We investigated the 21-carboxy-terminal peptide of C3a (C3a57-77) to see if it would cause pulmonary vascular constriction when infused into isolated buffer-perfused rat lungs. Injection of C3a57-77 (225 to 450 micrograms) caused mean pulmonary arterial pressure (Ppa) to rapidly increase. However, the response was transient, with Ppa returning to baseline within 10 min of its administration. C3a57-77 also resulted in an increase in lung effluent thromboxane B2 (TXB2), concomitant with the peak increase in Ppa. C3a57-77 did not affect the amount of 6-keto-PGF1 alpha in the same effluent samples. Indomethacin inhibited the C3a57-77-induced pulmonary artery pressor response and the associated TXB2 production. Indomethacin also decreased lung effluent 6-keto-PGF1 alpha. The thromboxane synthetase inhibitors CGS 13080 and U63,357 inhibited the C3a57-77-induced pulmonary artery pressor response and TXB2 production without affecting 6-keto-PGF1 alpha. These inhibitors did not inhibit pulmonary artery pressor responses to angiotensin II. Tachyphylaxis to C3a57-77 occurred because a second dose of C3a57-77 administered to the same lung failed to cause a pulmonary artery pressor response or TXB2 production. The loss of the pressor response was not due to a C3a57-77-induced decrease in pulmonary vascular responsiveness because pressor responses elicited by angiotensin II were not altered by lung contact with C3a57-77. Thus, C3a57-77 caused thromboxane-dependent pulmonary vascular constriction in isolated buffer perfused rat lungs.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Blocking of passive sensitization of human mast cells and basophil granulocytes with IgE antibodies by a recombinant human epsilon-chain fragment of 76 amino acids.

The recombinant peptide corresponding to residues 301-376 at the junction of constant regions 2 and 3 of the human IgE epsilon chain blocked the in vivo passive sensitization of human skin mast cells and in vitro sensitization of human basophil granulocytes with human IgE antibodies. An injection of the recombinant peptide or E myeloma protein into normal skin sites 1 hr before sensitization with an allergic serum blocked passive sensitization. In this system, approximately 10-fold higher molar concentration of the recombinant peptide than E myeloma protein was required for 50% inhibition of Prausnitz-Küstner reactions. When the mononuclear cells of two normal individuals were preincubated with the recombinant peptide or E myeloma protein for 15 min before passive sensitization with the same allergic serum and the cells were challenged with an optimal concentration of an antigen, approximately 11- to 13-fold higher concentration of the recombinant peptide than E myeloma protein was required for 50% inhibition of antigen-induced histamine release. Further studies with several recombinant peptides indicated that amino acid resides 363-376 in the Fc epsilon-chain fragment are not essential for binding of the peptide to Fc epsilon-chain receptor I.

Base Sequence↗
PubMed1989

Effect of monoclonal antihuman IgE on recombinant IgE(301-376) inhibition of specific IgE histamine release.

To explore the binding domains of rCIgE(301-376) necessary for inhibition of passive transfer of rye grass and Chinese elm IgE to human basophils, we employed monoclonal antibodies known to bind to IgE(301-336), M-272, and to IgE(367-376), M-27. By preincubating M-272, but not M-27, with rCIgE(301-376), passive transfer of specific IgE to basophils was partially inhibited. This implies that M-272 recognizes a binding site on rCIgE(301-376) or sterically interferes with the rCIgE(301-376) high-affinity binding domains on human basophils.

Allergens↗
PubMed1989

Inverse correlation of expiratory lung flows and sputum eosinophils in status asthmaticus.

Seventy-six consecutive patients admitted to Los Angeles County General Hospital with acute asthma were studied. Blood and sputum smears for cell counts were obtained on all patients within 12 hours of admission. Fifty-one (67%) patients were able or willing to perform spirometry and flow/volume curves in the first 24 hours of hospitalization. The severity of airway obstruction as assessed by forced expiratory volume in one second (FEV1), maximum mid-expiratory flow rate (MMFR), and forced vital capacity (FVC) was compared with blood and sputum eosinophil counts. Although there was no relation between the blood eosinophilia and airway obstruction, an inverse relationship between the number of eosinophils in the sputum and airway flow rates was observed. Higher percentages of sputum eosinophils were associated with diminished flow rates. We believe that sputum eosinophils may be helpful in the initial assessment of severe bronchial asthma.

Adolescent↗