RESUMEN
PROBLEM: RANTES (regulated upon activation, normal T cell expressed and secreted), is a chemokine with monocyte, macrophage, T lymphocyte, and eosinophil attractant and activating activities. This mediator has been detected in the peritoneal fluid of patients with endometriosis and in cultures of stromal cells from human endometrial and endometriotic tissue. To determine if endometrial epithelial cells were also a potential source of this mediator, primate endometrial epithelial cells were cultured in vitro and the constitutive and stimulated production of RANTES in these cultures was measured. METHOD OF STUDY: Uterine tissue was obtained from Macaca nemestrina monkeys and the endometrial epithelial cells were isolated and placed in culture for 24-72 hr. RANTES was measured in cell extracts and culture fluids by enzyme-linked immunosorbent assay (ELISA). RESULTS: Constitute release of RANTES was low, ranging from 28-52 ng/mL but addition of interferon gamma (INF-gamma) or the combination of IFN-gamma and tumor necrosis factor alpha (TNF-alpha) produced a marked increase in RANTES production. The greatest release, which was nearly 500-fold greater than the basal level, was observed at 72 hr with the combined addition of TNF-alpha and INF-gamma. Nearly 90% of the stimulated RANTES was released into culture fluids, while cell associated RANTES was minimal constituting only 11.2% of the total. CONCLUSION: These findings indicate that endometrial epithelial cells can produce and release RANTES. This chemokine may be an important attractant and activator of macrophages, T lymphocytes and/or eosinophils in the uterus during the reproductive cycle or implantation.
Asunto(s)
Quimiocina CCL5/biosíntesis , Endometrio/metabolismo , Células Epiteliales/metabolismo , Adyuvantes Inmunológicos/farmacología , Animales , Células Cultivadas , Quimiocina CCL5/metabolismo , Endometrio/efectos de los fármacos , Endometrio/ultraestructura , Células Epiteliales/efectos de los fármacos , Células Epiteliales/ultraestructura , Femenino , Interferón gamma/farmacología , Macaca nemestrina , Microscopía Electrónica de Rastreo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
RANTES is a chemokine with eosinophil attractant and activating activities. This study was undertaken to determine whether primary cultures of human nasal and primate bronchial epithelial cells produce RANTES and the effect of various cytokines and dexamethasone on the release of this chemokine. Nasal epithelial cells from 32 patients (HNE) and bronchial epithelial cells from 17 Macaca nemestrina monkeys (PBE) were cultured in vitro for 24 to 72 h with LPS, TNF-alpha, IL-1 beta, IFN-gamma and TNF-alpha combined with IFN-gamma and/or dexamethasone at 10 to 1000 micrograms/ml. Culture supernatants were assayed for RANTES by ELISA. RANTES synthesis was measured by immunoprecipitation. HNE and PBE released modest constitutive amounts of RANTES (350 to 1000 pg/ml) which did not increase with time in culture. Release of RANTES was stimulated by all activators except LPS in a time-dependent manner, with the greatest synthesis induced by the combined addition of TNF-alpha and IFN-gamma. The combination of these activators also increased RANTES synthesis as determined by immunoprecipitation. Dexamethasone at 100 and 1000 micrograms/ml produced significant inhibition of stimulated RANTES release. These data indicate that normal nasal and bronchial epithelial cells release RANTES which is upregulated by various cytokines and inhibited by dexamethasone. The enhanced release is due to stimulation of both synthesis and secretion. Production of RANTES by epithelial cells could contribute to the inflammation that characterizes the respiratory tract in asthma and rhinitis and downregulation of RANTES by glucocorticoids may be one mechanism of the therapeutic effect of these agents.
Asunto(s)
Bronquios/metabolismo , Quimiocina CCL5/metabolismo , Mucosa Nasal/metabolismo , Adulto , Animales , Bronquios/citología , Bronquios/efectos de los fármacos , Células Cultivadas , Quimiocina CCL5/antagonistas & inhibidores , Dexametasona/farmacología , Células Epiteliales , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Femenino , Humanos , Macaca nemestrina , Masculino , Persona de Mediana Edad , Mucosa Nasal/citología , Mucosa Nasal/efectos de los fármacos , Pruebas de PrecipitinaRESUMEN
PURPOSE/OBJECTIVE: To review the current use of strontium-89 (89Sr) to treat pain related to bony metastasis secondary to prostate cancer. DATA SOURCES: Published articles. DATA SYNTHESIS: Prostate cancer is the most commonly diagnosed cancer in the United States. The disease's most common site of metastasis is the bones. Bone metastasis leads to unrelenting pain. If healthcare providers are able to manage a patient's pain successfully, the patient's quality of life improves. CONCLUSION: When conventional therapies fail, 89Sr can be used as an alternative or an adjunct to pain management of bony metastasis in prostate cancer. IMPLICATIONS FOR NURSING PRACTICE: Nursing intervention primarily involves assessing pain, monitoring analgesics until 89Sr can begin to take effect, educating patients on using other medications with 89Sr, and assessing fatigue resulting from 89Sr-induced myelosuppression. As pain decreases, nurses also should monitor patients' activity levels, since they are at risk for pathologic fractures.