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Biomedical subjects

D B Bittleman

Publications and source records attributed to D B Bittleman.

8 recordsLinked to original sources
PubMed1996

Cytokines induce selective granulocyte chemotactic responses.

Neutrophils, eosinophils and cytokines are important in allergic airway inflammatory responses. However, it is unclear how cytokines selectively influence neutrophils versus eosinophils to migrate to an inflammatory site. The cytokines, transforming growth factor-beta1 (TGF-beta1), interleukin (IL)-1alpha, IL-5, IL-8, granulocyte macrophage-colony stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha), are released subsequent to allergic reactions and affect both neutrophil and eosinophil functions. We studied whether these cytokines differed in capacity to induce human neutrophil versus eosinophil migration through naked filters and human umbilical vein endothelial cell (HUVEC) and human pulmonary type II-like epithelial (A549) cell monolayers grown on filters. Dose-response experiments using all barriers were performed for each granulocyte and cytokine. TGF-beta1 did not induce granulocyte migration. IL-5 induced eosinophil migration only through naked filters. IL-1alpha stimulated neutrophil migration through cellular barriers, but not through naked filters. TNF-alpha and GM-CSF induced neutrophil and eosinophil migration through filters, but only neutrophil migration through cellular monolayers. Only IL-8 induced significant neutrophil and eosinophil migration; however, there were clear-cut differences between the neutrophilotactic and eosinophilotactic responses through all barriers employed. Thus, our data show that these cytokines induce distinct chemotactic responses for neutrophils versus eosinophils. Moreover, by using relevant cellular barriers versus naked filters, our data better examines the capability of these cytokines to induce selective granulocyte migration to an inflammatory site in lung diseases such as asthma.

Adult↗
PubMed1995

5-Hydroxyeicosatetraenoic acid (HETE)-induced neutrophil transcellular migration is dependent upon enantiomeric structure.

The 5(R) and 5(S) hydroxyeicosatetraenoic acids (5[R]-HETE, 5[S]-HETE) are important inflammatory mediators in lung diseases: they increase mucus, induce airway contraction, and potentiate neutrophil chemotaxis. Neutrophils are important cells in allergic and inflammatory lung diseases. Therefore, we examined the effects of both 5(R)-HETE and 5(S)-HETE on human neutrophil migration across naked filters and human umbilical vein endothelial (HUVE) cell and human type II-like pulmonary epithelial cell (A549) monolayers cultured on these filters. Time courses for both 5(R)-HETE and 5(S)-HETE show significant neutrophil migration at 40 min and maximal migration at 60 to 90 min through all three barriers. Checkerboard analysis showed that migration was chemotactic. Dose-response curves for both isomers through cellular monolayers had the same shapes, but 5(R)-HETE was more potent than 5(S)-HETE. There was greater migration through cellular barriers than through naked filters. Actinomycin D pretreatment of the cellular monolayers slightly inhibited the neutrophil transcellular chemotactic response to both 5-HETEs equally. Enhanced transcellular migration was not due to the production of a soluble chemotactic factor. Thus, although both isomers of 5-HETE were potent chemotactic agents, 5(R)-HETE was slightly more potent. Moreover, relevant endothelial and epithelial monolayers enhance both dose- and time-dependent neutrophil migration stimulated by 5(R)-HETE and 5(S)-HETE. These data indicate that (1) both 5(R)-HETE and 5(S)-HETE are important in mediating lung inflammatory processes, and (2) 5(R)-HETE may play a more important role in neutrophil-rich lung inflammatory responses than 5(S)-HETE because it is a more potent inducer of neutrophil migration through endothelial and epithelial barriers.

Cell Movement↗
PubMed1995

Interleukin-8 mediates interleukin-1 alpha-induced neutrophil transcellular migration.

Interleukin-1 alpha (IL-1 alpha) is a cytokine with a myriad of potent proinflammatory effects. Neutrophils are important immune effector cells in allergic and inflammatory lung diseases. We examined the effects of IL-1 alpha on human neutrophil migration across naked filters and human umbilical vein endothelial (HUVE) cell and type II-like pulmonary epithelial cell (A549) monolayers cultured on these filters. IL-1 alpha from 10(-13) to 10(-9) M induced dose-dependent neutrophil migration through both HUVE and A549 cellular monolayers but not through naked filters. Neutrophil migration was consistently greater through A549 monolayers compared with HUVE monolayers. IL-1 alpha-induced neutrophil migration was also time dependent, and the kinetics of neutrophil migration through HUVE and A549 monolayers were similar. Significant migration through either monolayer was not observed until 2 h, and maximal migration occurred at 3 h through A549 and 5 h though HUVE cellular monolayers. Supernatants of IL-1 alpha (10(-11) M)-stimulated HUVE and A549 monolayers induced significantly more migration of neutrophils across naked filters than 10(-11) M IL-1 alpha itself, suggesting the release of soluble secondary chemotactic factor(s). Pretreatment of HUVE and A549 monolayers with actinomycin D inhibited both IL-1 alpha-induced production of soluble chemotactic factor(s) and transcellular migration by > 90%. Supernatants from IL-1 alpha-treated HUVE and A549 cells contained significant concentrations of interleukin 8 (IL-8), and coincubation of these supernatants with anti-IL-8 inhibited approximately 50% of supernatant-induced chemotaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Movement↗
PubMed1994

Allergic models and cytokines.

Cytokines are proinflammatory protein mediators produced by many cells, including mast cells, T lymphocytes, eosinophils, airway epithelial cells, and macrophages. There are numerous in vitro and in vivo animal and human studies showing that cytokines are released as a result of allergic reactions. Cytokines mediate allergic inflammation by activating eosinophils, promoting mast cell development, regulating immunoglobulin isotype switching to immunoglobulin E, modulating adhesion molecule regulation, and promoting both neutrophil and eosinophil chemotaxis. Furthermore, there are data that show the pro-inflammatory effects of cytokines may be blocked by cytokine antagonists. This report reviews the in vitro and in vivo animal and human studies of allergic models of cytokine production and regulation. It also discusses the specific roles of cytokines in the allergic inflammatory response and asthma.

Animals↗
PubMed1994

Abnormal movement of the arytenoid region during exercise presenting as exercise-induced asthma in an adolescent athlete.

A 16-year-old female basketball player presented with a 2 1/2-year history of exercise-induced severe dyspnea, stridor, and mild wheezing that did not respond to prophylactic treatment with beta-agonists and cromolyn. Spirometric data at rest were normal, but flow-volume loops during exercise suggested a variable extrathoracic obstruction. Laryngoscopic evaluation while the patient was riding an exercise bicycle demonstrated an abnormal motion of the arytenoid region causing obstruction of the airway during inspiration. The vocal cords moved normally. This patient demonstrates the capacity of supraglottic tissue to obstruct the airway during exercise as a cause for exercise-induced dyspnea and stridor. Patients with this disorder may be misdiagnosed as having exercise-induced asthma.

Adolescent↗