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1.
Exp Appl Acarol ; 60(2): 127-38, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23238958

RESUMEN

Tomato plants have their leaves, petioles and stems covered with glandular trichomes that protect the plant against two-spotted spider mites and many other herbivorous arthropods, but also hinder searching by phytoseiid mites and other natural enemies of these herbivores. This trichome cover creates competitor-free and enemy-free space for the tomato russet mite (TRM) Aculops lycopersici (Acari: Eriophyidae), being so minute that it can seek refuge and feed inbetween the glandular trichomes on tomato cultivars currently used in practice. Indeed, several species of predatory mites tested for biological control of TRM have been reported to feed and reproduce when offered TRM as prey in laboratory experiments, yet in practice these predator species appeared to be unable to prevent TRM outbreaks. Using the phytoseiid mite, Amblydromalus limonicus, we found exactly the same, but also obtained evidence for successful establishment of a population of this predatory mite on whole plants that had been previously infested with TRM. This successful establishment may be explained by our observation that the defensive barrier of glandular plant trichomes is literally dropped some time after TRM infestation of the tomato plants: the glandular trichome heads first rapidly develop a brownish discoloration after which they dry out and fall over onto the plant surface. Wherever TRM triggered this response, predatory mites were able to successfully establish a population. Nevertheless, biological control was still unsuccessful because trichome deterioration in TRM-infested areas takes a couple of days to take effect and because it is not a systemic response in the plant, thereby enabling TRM to seek temporary refuge from predation in pest-free trichome-dense areas which continue to be formed while the plant grows. We formulate a hypothesis unifying these observations into one framework with an explicit set of assumptions and predictions to be tested in future experiments.


Asunto(s)
Ácaros/fisiología , Hojas de la Planta/anatomía & histología , Hojas de la Planta/parasitología , Solanum lycopersicum/parasitología , Tricomas/parasitología , Animales , Femenino , Herbivoria , Oviposición , Conducta Predatoria
2.
J Clin Invest ; 87(3): 838-41, 1991 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1705566

RESUMEN

Tumor necrosis factor (TNF) inhibits granulocyte-colony-stimulating factor (G-CSF)-induced human acute myeloid leukemia (AML) growth in vitro. Incubation of blasts from three patients with AML in serum-free medium with TNF (10(3) U/ml), and subsequent binding studies using 125I-G-CSF reveal that TNF downregulates the numbers of G-CSF receptors by approximately 70%. G-CSF receptor numbers on purified blood granulocytes are also downmodulated by TNF. Downregulation of G-CSF receptor expression becomes evident within 10 min after incubation of the cells with TNF at 37 degrees C and is not associated with an apparent change of the dissociation constant (Kd). The TNF effect does not occur at 0 degrees C and cannot be induced by IL-2, IL-6, or GM-CSF. TNF probably exerts its effect through activation of protein kinase C (PKC) as the TNF effect on G-CSF receptor levels can be mimicked by 12-O-tetradecanoylphorbol-13- acetate. The PKC inhibitor Staurosporine (Sigma Chemical Co., St. Louis, MO) as well as protease inhibitors can completely prevent G-CSF receptor downmodulation. Thus, it appears TNF may act as a regulator of G-CSF receptor expression in myeloid cells and shut off G-CSF dependent hematopoiesis. The regulatory ability of TNF may explain the antagonism between TNF and G-CSF stimulation.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/metabolismo , Granulocitos/fisiología , Leucemia Mieloide/metabolismo , Receptores de Factor Estimulante de Colonias de Granulocito/genética , Factor de Necrosis Tumoral alfa/farmacología , Enfermedad Aguda , Alcaloides/farmacología , Regulación hacia Abajo/efectos de los fármacos , Granulocitos/efectos de los fármacos , Humanos , Técnicas In Vitro , Inhibidores de Proteasas/farmacología , Estaurosporina , Acetato de Tetradecanoilforbol/farmacología , Factores de Tiempo
3.
Leukemia ; 7(3): 426-34, 1993 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7680401

RESUMEN

We have investigated the stimulative effects of mast cell growth factor (MGF) in primary acute myeloid leukemia (AML) in vitro. MGF stimulated DNA synthesis of purified leukemic blasts in eight out of 10 cases and colony formation in four cases in serum-free (SF) culture. MGF synergized with interleukin-3 (IL-3; four out of 10 cases), granulocyte-macrophage colony-stimulating factor (GM-CSF; three out of 10 cases), granulocyte colony-stimulating factor (G-CSF; six out of 10 cases), macrophage colony-stimulating factor (M-CSF; one out of 10 cases) and erythropoietin (EPO; one out of 10 cases) when added to culture in combination. Synergistic effects of MGF in combination with other CSFs were also seen in the colony assay. Antibodies against GM-CSF, M-CSF, G-CSF, and IL-6 did not inhibit the MGF response, suggesting that the stimulative effect of MGF was not mediated through autocrine release of those cytokines. Cell recovery data in liquid cultures that contained MGF, IL-3, or MGF + IL-3, indicated that both MGF and IL-3 augmented the maintenance of clonogenic cells as compared to nonsupplemented cultures, but the effect of the combination of IL-3 + MGF did not show synergy. In contrast, activation of DNA synthesis by MGF was abrogated in the presence of tumor necrosis factor (TNF; four out of 10 cases) and interleukin-4 (IL-4; two out of 10 cases). Fluorescence-activated cell sorting (FACS) analysis with anti c-kit antibodies revealed MGF receptor expression in eight out of nine cases, often in a subpopulation of the cells. Scatchard analysis of MGF receptors in two cases indicated the presence of 1460 and 41,500 (mean) binding sites, respectively, of high affinity (Kd 40-160 pmol/l). The MGF dose-response curve in the presence of IL-3 or GM-CSF resulted in a higher plateau of DNA synthesis, however no shift in the dose response was apparent. The respective reciprocal dose response relations to GM-CSF, IL-3, or G-CSF were similarly elevated when MGF was added. MGF did not alter IL-3 and GM-CSF receptor expression, nor did IL-3, GM-CSF, G-CSF, TNF, or IL-4 influence MGF binding to AML cells.(ABSTRACT TRUNCATED AT 400 WORDS)


Asunto(s)
Citocinas/farmacología , Factores de Crecimiento de Célula Hematopoyética/farmacología , Leucemia Mieloide/tratamiento farmacológico , Enfermedad Aguda , Anticuerpos/farmacología , División Celular/efectos de los fármacos , División Celular/fisiología , Interacciones Farmacológicas , Sinergismo Farmacológico , Factor Estimulante de Colonias de Granulocitos/farmacología , Factores de Crecimiento de Célula Hematopoyética/inmunología , Factores de Crecimiento de Célula Hematopoyética/fisiología , Humanos , Interleucina-3/farmacología , Leucemia Monocítica Aguda/tratamiento farmacológico , Leucemia Monocítica Aguda/patología , Leucemia Mieloide/patología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Aguda/patología , Proteínas Proto-Oncogénicas/efectos de los fármacos , Proteínas Proto-Oncogénicas/fisiología , Proteínas Proto-Oncogénicas c-kit , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos de los fármacos , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/fisiología , Receptores de Interleucina-3/efectos de los fármacos , Receptores de Interleucina-3/fisiología , Sensibilidad y Especificidad , Factor de Células Madre , Células Tumorales Cultivadas/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos
4.
Leuk Res ; 13(11): 973-80, 1989.
Artículo en Inglés | MEDLINE | ID: mdl-2481793

RESUMEN

Recent studies have suggested that interleukin-2 (IL-2), tumor necrosis factor (TNF) and a crude preparation of B-cell growth factors (BCGF) have a regulatory role in the proliferation of B-CLL cells. However, interpretation of the experimental data has been complicated by potential methodological pitfalls. To establish the role of these factors in B-CLL growth, we investigated their stimulatory effects under accurately defined in vitro conditions. Purified B-CLL cells were obtained by fluorescence activated cell sorting on the basis of coexpression of CD5 and CD19/CD20/CD24 surface antigens in order to avoid interference of normal cell contamination. Subsequently, the cells were cultured free of serum. TNFs alpha and beta and BCGF induced DNA synthesis in the purified B-CLL cells in five out of six cases, as assessed by 3H-thymidine (TdR) uptake on days 3 and 6 of culture. The stimulating activity of BCGF could be suppressed by the addition of specific anti-TNF monoclonal antibodies, indicating that the BCGF activity had been, to a major extent, due to the presence of TNFs in this impure preparation. IL-2, when added as a single stimulus, induced DNA synthesis in the B-CLL cells in three out of six cases on day 3, but not on day 6 of culture. In some patients, cooperative effects of IL-2 and TNF were observed. Cytogenetic analysis was applied to confirm the CLL origin of the proliferating cells. The phorbol ester TPA or anti-IgM were not required for induction of DNA synthesis in the CLL cells, although TPA potentiated 3H-TdR uptake in three out of six cases, and anti-IgM in one case. Our data demonstrate that IL-2 and TNFs alpha and beta can act as growth factors for B-CLL cells under fully defined in vitro conditions, essentially without the need of TPA or anti-IgM as primary activation signals.


Asunto(s)
Linfocitos B/patología , Interleucina-2/farmacología , Leucemia Linfocítica Crónica de Células B/patología , Linfotoxina-alfa/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Antígenos CD/análisis , Antígenos CD19 , Antígenos de Diferenciación/análisis , Antígenos de Diferenciación de Linfocitos B/análisis , Antígenos CD5 , División Celular/efectos de los fármacos , Humanos , Técnicas Inmunológicas , Interleucina-4/farmacología , Cariotipificación , Receptores de Antígenos de Linfocitos B/fisiología , Acetato de Tetradecanoilforbol/farmacología , Células Tumorales Cultivadas
5.
Blood ; 75(7): 1439-45, 1990 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-2156580

RESUMEN

Granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) control the proliferation of human acute myeloid leukemia (AML) cells in vitro. Previously, we have shown that receptors for GM-CSF and IL-3 are often coexpressed on AML cells. Here we present experiments with purified AML blasts, normal monocytes, and granulocytes that were conducted to analyze the properties of GM-CSF and IL-3 binding proteins in more detail. On AML cells from eight cases we demonstrate two types of GM-CSF receptors: one with low affinity (dissociation constant [kd] 5.1 to 24.8 nmol/L) and one with a high affinity (kd 31 to 104 pmol/L). These AML cells also expressed high affinity receptors for IL-3 (kd 24 to 104 pmol/L). Cross-competition experiments showed that an excess concentration of nonlabeled IL-3 completely prevented the high affinity binding of radiolabled GM-CSF. This competition occurred at 37 degrees C as well as 4 degrees C. Low affinity GM-CSF binding was not affected by IL-3. Binding of radiolabeled IL-3 could be prevented by nonlabeled GM-CSF. In certain cases, this competition was complete, whereas in others only partial (49% to 77%) reduction of the radiolabeled IL-3 binding was seen. On the basis of these ligand binding features, we propose the existence of three receptor types on AML cells: (1) low affinity GM-CSF receptors that do not bind IL-3, (2) dual high affinity GM-CSF/IL-3 receptors, and (3) high affinity IL-3 receptors that do not bind GM-CSF. We could also demonstrate these receptor types on normal monocytes. In addition, a fourth type of receptor was apparent on normal granulocytes (4), incapable of binding IL-3 and with an intermediate affinity for GM-CSF (approximately 400 pmol/L). Chemical crosslinking showed that GM-CSF and IL-3 both bind to proteins with molecular weight values of 130, 105, and 75, which provides additional evidence for the existence of a common GM-CSF/IL-3 receptor complex.


Asunto(s)
Factores Estimulantes de Colonias/metabolismo , Sustancias de Crecimiento/metabolismo , Interleucina-3/metabolismo , Leucemia Mieloide Aguda/metabolismo , Monocitos/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos/metabolismo , Unión Competitiva , Membrana Celular/inmunología , Membrana Celular/metabolismo , Factores Estimulantes de Colonias/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Sustancias de Crecimiento/farmacología , Humanos , Cinética , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/inmunología , Peso Molecular , Monocitos/inmunología , Receptores de Superficie Celular/efectos de los fármacos , Receptores de Superficie Celular/aislamiento & purificación , Receptores del Factor Estimulante de Colonias , Receptores de Interleucina-3 , Proteínas Recombinantes/metabolismo , Termodinámica
6.
Blood ; 77(5): 989-95, 1991 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-1825289

RESUMEN

Tumor necrosis factor (TNF) acts as a potent enhancer of granulocyte-macrophage colony-stimulating factor (GM-CSF)- and interleukin-3 (IL-3)-induced human acute myeloid leukemia (AML) growth in vitro. We have analyzed the effects of TNF alpha on the expression of GM-CSF and IL-3 receptors on AML cells. Incubation of blasts from seven patients with AML in serum-free medium with TNF (10(3) U/mL) and subsequent binding studies using 125I-GM-CSF and 125I-IL-3 show that TNF increases the specific binding of GM-CSF (30% to 280%) and IL-3 (40% to 600%) in all cases. From Scatchard plot analysis it appears that TNF upregulates (1) low-affinity GM-CSF binding sites, (2) common high-affinity IL-3/GM-CSF binding sites, and (3) unique (non-GM-CSF binding) IL-3 binding sites. The effect of TNF is dose dependent and is half maximal at a concentration of 100 U/mL, and becomes evident at 18 hours of incubation with TNF at 37 degrees C, but not at 0 degree C. The GM-CSF dose-response curve of AML-colony-forming units plateaus at a higher level in the presence of TNF, which indicates that additional numbers of cells become responsive to GM-CSF. Incubation of AML blasts with the phorbol ester 12-0-tetradecanoylphorbol-13-acetate or formyl-Met-Leu-Phe (protein kinase C activators) does not influence GM-CSF receptor expression, suggesting that receptor upregulation by TNF is not mediated through activation of protein kinase C. On the other hand, the protein synthesis inhibitor cycloheximide abrogates receptor upregulation induced by TNF. In contrast to these findings in AML, TNF does not upregulate GM-CSF receptor numbers on blood granulocytes or monocytes. We conclude that TNF exerts positive effects on growth factor receptor expression of hematopoietic cells.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Leucemia Monocítica Aguda/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mielomonocítica Aguda/metabolismo , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Receptores de Interleucina-3/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Cicloheximida/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Técnicas In Vitro , Interleucina-3/metabolismo , Proteína Quinasa C/metabolismo , Regulación hacia Arriba/efectos de los fármacos
7.
J Biol Chem ; 268(14): 10154-9, 1993 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-8486685

RESUMEN

Acute myeloid leukemia blasts express dual affinity (high and low) granulocyte-macrophage colony-stimulating factor (GM-CSF) binding, and the high affinity GM-CSF binding is counteracted by excess interleukin-3 (IL-3). Neutrophils express a single class of GM-CSF-R with intermediate affinity that lack IL-3 cross-reactivity. Here we demonstrate the differentiation associated changes of GM-CSF binding characteristics in three models representative of different stages of myeloid maturation. We find that high affinity GM-CSF binding is converted into intermediate affinity binding, which still cross-reacts with IL-3, beyond the stage of promyelocytes. During terminal maturation towards neutrophils, IL-3 cross-reactivity is gradually lost. We sought to determine the mechanism underlying the affinity conversion of the GM-CSF-R. Northern and reverse transcriptase-polymerase chain reaction analysis of GM-CSF-R alpha and -beta c (KH97) transcripts did not provide indications for the involvement of GM-CSF-R splice variants in the formation of the intermediate affinity GM-CSFR complex. In COS-cell transfectants with increasing amounts of beta c in the presence of a fixed number of GM-CSF-R alpha chains, the high affinity GM-CSF binding converted into intermediate affinity GM-CSF binding. These results are discussed in view of the concept that increasing expression of beta c subunits may cause alternative oligomerization of the GM-CSF-R alpha and -beta c subunits resulting in the formation of intermediate rather than high affinity GM-CSFR alpha.beta c complexes.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mieloide/metabolismo , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Enfermedad Aguda , Animales , Secuencia de Bases , Línea Celular , Humanos , Cinética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mieloide/patología , Leucemia Promielocítica Aguda , Sustancias Macromoleculares , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Reacción en Cadena de la Polimerasa/métodos , ARN Neoplásico/genética , ARN Neoplásico/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Eliminación de Secuencia , Transcripción Genética , Transfección , Tretinoina/farmacología , Células Tumorales Cultivadas , Regulación hacia Arriba
8.
Blood ; 89(5): 1690-700, 1997 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-9057652

RESUMEN

Patients with myelodysplastic syndrome (MDS) have ineffective in vivo and in vitro erythropoiesis, characterized by an impaired response to erythropoietin (Epo). We examined proliferation and maturation of MDS marrow cells in response to Epo in more detail. Epo-dependent DNA synthesis as well as induction of GATA-1 binding activity in marrow cells from 15 MDS cases were severely reduced as compared with normal bone marrow (NBM). Additionally, the appearance of morphologically identifiable erythroid cells was decreased in MDS cell cultures. These data indicate that both the Epo-dependent proliferation as well as the differentiation induction by Epo is suppressed. To study more upstream events of the Epo signal transduction route we investigated activation of the signal transducer and activator of transcription (STAT) 5. In all 15 MDS samples tested, STAT5 activation was absent or greatly suppressed in response to Epo. In contrast, interleukin-3 induced a normal STAT5 response in MDS cells. Further, in MDS the subset of CD71+ BM cells that is phenotypically similar to Epo-responsive cells in normal marrow, was present. We conclude that the Epo response in MDS is disturbed at an early point in the Epo-receptor (EpoR) signal transduction pathway.


Asunto(s)
Médula Ósea/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Eritropoyetina/farmacología , Proteínas de la Leche , Síndromes Mielodisplásicos , Transducción de Señal/efectos de los fármacos , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/metabolismo , Médula Ósea/patología , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , Factores de Unión al ADN Específico de las Células Eritroides , Femenino , Factor de Transcripción GATA1 , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Factor de Transcripción STAT5
9.
Blood ; 75(11): 2097-101, 1990 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-2189505

RESUMEN

We investigated the proliferation-inducing effects of human recombinant interleukin-7 (IL-7) on acute lymphoblastic leukemia (ALL) cells. It is shown that IL-7 stimulates DNA synthesis in ALL cells of B-cell precursor (n = 5) as well as immature T-cell origin (n = 2). Cytogenetic analysis of the cells of four patients proliferating in IL7-supplemented cultures established the leukemic descendence of the IL-7-responsive cells. 125I-IL-7 binding experiments with the cells of one patient and with two ALL cell lines showed the presence of two types of IL-7 receptors: one with a high affinity (kd 29 to 51 pmol/L) and one with a low affinity (kd 2.3 to 76 nmol/L) for the ligand. We conclude that IL-7 is one of the cytokines involved in the complex regulation of ALL cell proliferation.


Asunto(s)
Linfoma de Burkitt/patología , Sustancias de Crecimiento/farmacología , Interleucina-7/farmacología , Leucemia Linfoide/patología , Linfocitos B/efectos de los fármacos , Linfocitos B/patología , Linfocitos B/ultraestructura , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/patología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Interleucina-7/metabolismo , Masculino , Receptores Inmunológicos/metabolismo , Receptores de Interleucina-7 , Células Madre/efectos de los fármacos , Células Madre/patología , Células Madre/ultraestructura , Linfocitos T/efectos de los fármacos , Linfocitos T/patología , Linfocitos T/ultraestructura , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/patología
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