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At least 919 records · Page 51Linked to original sources
PubMed1999

Activity-dependent modulation of rod photoreceptor cyclic nucleotide-gated channels mediated by phosphorylation of a specific tyrosine residue.

Cyclic nucleotide-gated (CNG) channels are crucial for phototransduction in vertebrate rod photoreceptors. The cGMP sensitivity of these channels is modulated by diffusible intracellular messengers, including Ca2+/calmodulin, contributing to negative feedback during sensory adaptation. Membrane-associated protein tyrosine kinases and phosphatases also modulate rod CNG channels, but whether this results from direct changes in the phosphorylation state of the channel protein has been unclear. Here, we show that bovine rod CNG channel alpha-subunits (bRET) contain a tyrosine phosphorylation site crucial for modulation. bRET channels expressed in Xenopus oocytes exhibit modulation, whereas rat olfactory CNG channels (rOLF) do not. Chimeric channels reveal that differences in the C terminus, containing the cyclic nucleotide-binding domain, account for this difference. One specific tyrosine in bRET (Y498) appears to be crucial; replacement of this tyrosine in bRET curtails modulation, whereas installation into rOLF confers modulability. As the channel becomes dephosphorylated, there is an increase in the rate of spontaneous openings in the absence of ligand, indicating that changes in the phosphorylation state affect the allosteric gating equilibrium. Moreover, we find that dephosphorylation, which favors channel opening, requires open channels, whereas phosphorylation, which promotes channel closing, requires closed channels. Hence, modulation by changes in tyrosine phosphorylation is activity-dependent and may constitute a positive feedback mechanism, contrasting with negative feedback systems underlying adaptation.

Adenosine Triphosphate↗
PubMed2000

Considering the alternatives: a special study module in complementary therapy.

OBJECTIVES: This study sought to describe the motivation, experience and attitude change of 21 undergraduate medical students who chose a special study module in complementary therapy (CT). DESIGN: Survey; self-administered questionnaire before and after the module. SETTING: Second year medical students' course special study module in CT concentrating on homeopathy at The University of Birmingham Medical School, UK. RESULTS: Twenty questionnaires were completed at each time point with 19 sets of paired data. Students saw the module as offering a rare opportunity to examine and evaluate non-orthodox therapies. Eleven students had personal experience of a CT prior to the module, but there was a wide range of student attitudes from 'scepticism' to 'acceptance'. Students tended to rate the efficacy of CT as a whole, and homeopathy in isolation, similarly (P = 0.005). This trend was less marked at the end (P = 0.077). On both occasions CT was rated higher. Individual student's ratings moved in both directions. Twelve students considered learning and practising a CT, most commonly acupuncture. CONCLUSIONS: The evolution of UK undergraduate medical curricula has begun to incorporate non-core components through special study modules. The Birmingham CT module was popular and attracted students with a range of initial attitudes. We have demonstrated that it allowed a process of discernment about the value and role of CT within the established medical system whilst maintaining heterogeneity of opinion.

Attitude↗
PubMed2000

Development of a hybrid artificial liver using a polyurethane foam/hepatocyte-spheroid packed-bed module.

Primary dog hepatocytes spontaneously formed spheroids in the pores of polyurethane foam (PUF) within 1-2 days of stationary culture. The spheroids, about 100-150 microm in diameter, partly attached to the surface and immobilized inside these pores. The lidocaine disappearance rate decreased to about 4 microg/10(5) viable cells/day for 10 days, while in the PUF/spheroid culture the rate was maintained at almost the initial level of 8 microg/10(5) viable cells/day for 10 days. Then, two scales of PUF packed-bed modules were designed. A small module (PUF volume; 14.5 cm3) was used for in vitro culture to investigate optimum culture conditions, and a large module (PUF volume; 300 cm3) was designed for dog experiments. Hepatocytes inoculated in these modules also formed spheroids and maintained almost the same activity of albumin secretion rate (111 microg/cm3 PUF/day in the small module and 87.7 microg/cm3 PUF/day in the large module). These results indicate that the PUF packed-bed module containing hepatocyte-spheroids is promising as a hybrid artificial liver.

Albumins↗
PubMed1998

Design parameters of flat-panel LED modules for plant lighting applications.

Semispherical high-intensity light-emitting diodes (LEDS) mounted on a circuit board have been developed and examined for plant growth applications. This type of LED configuration, however, has problems such as relatively poor heat dissipation, difficulty of effecting high light uniformity, and high cost of assembly. Such problems may now be obviated through use of the recently developed flat-panel LED modules. In this study, the photosynthetic photon flux (PPF) levels and PPF distribution of 172 x 27 mm red flat-panel LED modules were determined. Results showed that: 1) the red flat-panel LED modules tested produced a mean PPF level of about 111 micromoles m-2 s-1 at a distance of 10 cm, which would be adequate for most micropropagated species grown photomixotrophically and reasonable for some micropropagated species grown photoautotrophically, both in terms of red wavelength; 2) the mean surface PPF of 419 micromoles m-2 s-1 for a single LED in a flat-panel module was about 47% greater than that for a single semispherical LED at about equal operational currents, owing primarily to the significantly larger reflectance area present in a flat-panel LED than that in a semispherical LED; 3) two flat-panel LED modules tested had about 80% of their illuminated areas having PPF values equal to or greater than half their maximum PPF levels, whereas the third module had a corresponding figure of about 67%; and 4) flat-panel LED modules exhibited very similar PPF distributions, underscoring the advantage of the LED flat-panel design over the manually assembled LED array in the ease of replicating light distributions.

Ecological Systems, Closed↗
PubMed2002

Clinical development of P glycoprotein modulators in oncology.

The last two decades have witnessed dramatic advances into the mechanisms of drug resistance in cancer. The identification of P glycoprotein (Pgp) as a specific mechanism led to the initial hope and expectation that it would be possible to modulate this and increase sensitivity to drug therapy. Clinical trials using first- and second-generation Pgp modulators did establish proof of principle that in some settings, clinical drug resistance could be overcome with the addition of a Pgp modulator-for example, clinical resistance to paclitaxel, a Pgp substrate, in women with ovarian cancer was shown to be overcome in approximately 20% with the addition of PSC 833, a highly effective Pgp modulator. However, evolutionary and adaptive redundancy in resistance mechanisms have tempered clinical results, even with very effective second- and third-generation modulators. The lessons from oncology establish sound methodology for the evaluation of Pgp modulators for safety, tolerability and efficacy in Phase I, II and III clinical trials. This review will focus on some of the early-phase clinical trials with earlier and newer Pgp modulators, either as single agents or in combination with chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Brain region-specific mechanisms for acute morphine-induced mitogen-activated protein kinase modulation and distinct patterns of activation during analgesic tolerance and locomotor sensitization.

Opioid-receptor activation in cell lines results in phosphorylation of p42/44 mitogen-activated protein kinase (MAPK), which contributes to agonist-induced desensitization of adenylate cyclase signaling. In this study, morphine-induced MAPK modulation was examined in the mouse brain using antibodies against phosphorylated MAPK. Thirty minutes after systemic morphine, MAPK modulation was observed in brain areas associated with analgesia and reward. Activation of MAPK was increased in the anterior cingulate (Acc), somato-sensory and association cortices, and locus ceruleus (LC). In contrast, MAPK activation was decreased in the nucleus accumbens and central amygdala (CeA). Double-label confocal microscopy revealed that morphine-induced MAPK modulation occurred predominantly in cells not expressing mu-opioid receptors, with the exception of the LC. Furthermore, the NMDA receptor antagonist 3,3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonate blocked morphine-induced MAPK modulation in several cortical areas including the Acc. We then examined morphine-induced MAPK modulation during expression of either analgesic tolerance or locomotor sensitization, which were differentiated by two repeated morphine regimens. Analgesic tolerance was accompanied by tolerance to morphine-induced MAPK modulation in all of the brain areas examined except the CeA. Locomotor sensitization resulted in sensitization to morphine-induced MAPK activation in the posterior basolateral amygdala. Additionally, a pronounced instatement of morphine-induced MAPK activation was observed in CA3 hippocampal processes. This instatement was observed during expression of tolerance; however, it was not significant during sensitization. In summary, these results provide distinct, region-specific mechanisms for morphine-induced MAPK modulation in the mouse brain and give insight into the brain circuitry involved in acute and adaptive opioid behaviors.

Analgesics, Opioid↗
PubMedDate not supplied

[Natural modulators of the function of the amine oxidase system in the body].

In cerebrospinal fluid (CSF) obtained from patients with chronic alcoholism natural modulators of monoamine oxidase (MAO) activity, containing in human mitochondrial and microsomal fractions or in rat brain mitochondria, have been found. These modulators, which were previously unknown, did not affect the activity of partially purified diamine oxidase from human placenta with 14C-putrescine as a substrate. The MAO modulators from CSF were thermostable (during 3 min at 100 degrees), penetrated through dialysing membrane thus differing from high molecular modulators of MAO previously described. In the system containing membrane bound MAO from human placenta, where the MAO-A is predominating, the modulators studied mostly inhibited deamination of 14C-serotonin. However, in the system containing membrane bound MAO from rat brain with prevalence of the MAO-B, the modulators from human CSF caused either inhibition or stimulation of oxidative deamination of 14C-serotonin or 14C-beta-phenylethylamine used as substrates. The modulators studied were not similar to tribulin (isatin) or quinolinic acid in their effects on catalytic properties of the amine oxidases investigated.

Adult↗
PubMedDate not supplied

Novel small molecule cyclin-dependent kinases modulators in human clinical trials.

Aberrations in cell cycle control occurs in the majority of human malignancies due to inactivation of tumor suppressor gene Rb by the phosphorylation induced by "hyperactive" cyclin-dependent kinases. Thus, it is quite reasonable to design cdk modulators for the prevention and treatment of human neoplasms. In order to target the cdk complexes, 2 main strategies were considered: to target the ATP binding site of cdks (direct cdk modulators) and to target upstream pathways required for cdk activation (indirect cdk modulators). Examples for the first group include flavopiridol, roscovitine, BMS-387032. Examples for the second group include perifosine, lovastatin, UCN-01. The first example of a direct small molecule cdk modulator tested in the clinic, flavopiridol, is a pan-cdk inhibitor that not only promotes cell cycle arrest but also halts transcriptional elongation, promotes apoptosis, induces differentiation and has antiangiogenic properties. Clinical trials with this agent were performed with at least 3 different schedules of administration: 1 hour infusion, 24 hour infusion and 72 hour infusion. Main toxicities for infusions >/=24 hours are secretory diarrhea and pro-inflammatory syndrome. In addition, patients receiving shorter infusions have nausea/vomiting and neutropenia. Some clinical responses were observed in several patients with refractory malignancies. Based on these encouraging results, a Phase 3 trial comparing standard combination chemotherapy versus combination chemotherapy plus flavopiridol is currently under investigation. The second example of direct small molecule cdk modulator tested in clinical trials is UCN-01 (7-hydroxi-staurosporine). UCN-01 has interesting preclinical features: inhibits ca2+-dependent PKCs, promotes apoptosis, arrest cell cycle progression at G1/S and abrogates checkpoints upon DNA damage. The first Phase I trial of UCN-01 demonstrated a very prolonged half-life. Based on this novel feature, UCN-01 is administered as a 72 hour continuous infusion every 4 weeks (second and subsequent cycles UCN-01 is administered as a 36-hour infusion). Other shorter schedules (i.e., 3 hours) are being tested. Dose-limiting toxicities include nausea/vomiting, hypoxemia and insulin-resistant hyperglycemia. Combination trials with cisplatin and other DNA-damaging agents are being tested. Recently, Phase I trials with two novel small molecule cdk modulators, BMS 387032 and R-Roscovitine (CYC202), have commenced with good tolerability. Phase 2 trials and Phase I trials in combination with standard chemotherapy is being planned with these agents. In summary, novel small molecule cdk modulators are being tested in the clinic with interesting results. Although these small molecules are directed towards a very prevalent cause of carcinogenesis, we need to test them in advanced clinical trials to determine the future of this class of agents for the prevention and therapy of human malignancies.

Adenosine Triphosphate↗
PubMed1991

Influence of recombinant gamma-aminobutyric acid-A receptor subunit composition on the action of allosteric modulators of gamma-aminobutyric acid-gated Cl- currents.

gamma-Aminobutyric acid (GABA)-activated Cl- currents in neonatal rat cortical neurons and in cultured cells engineered for the expression of specific molecular forms of the GABAA receptor alpha, beta, and gamma subunits, were recorded with the patch-clamp technique in the whole-cell configuration. The effects of various allosteric modulators of GABAA receptors were determined. Diazepam and clonazepam showed greater efficacy as positive modulators of GABA-elicited currents in alpha 2 beta 1 gamma 2 or alpha 3 beta 1 gamma 2 receptors than in alpha 1 beta 1 gamma 2 or alpha 5 beta 1 gamma 2 receptors or in cortical neurons. Alpidem was more efficacious at alpha 1 beta 1 gamma 2 or alpha 2 beta 1 gamma 2 receptors than at alpha 1 beta 1 gamma 2 or alpha 5 beta 1 gamma 2 receptors or in cortical neurons. Conversely, zolpidem was equally efficacious for all these receptors except for alpha 5 beta 1 gamma 2. Both imidazopyridines (alpidem and zolpidem) were virtually ineffective at modulating the GABA response of alpha 5 beta 1 gamma 2 receptors and in almost all the receptors assembled from alpha 1, alpha 2, alpha 3 or alpha 5 subunits together with beta 1 and gamma 1 subunits. The beta-carboline derivatives methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and methyl-beta-carboline-3-carboxylate (beta-CCM) elicited a positive allosteric modulation of alpha 1 beta 1 gamma 1 or alpha 2 beta 1 gamma 1 receptors, whereas they acted as negative allosteric modulators at nearly all other receptors tested, as they do in cortical neurons. Although the positive allosteric modulation by beta-carbolines never exceeded a doubling of the GABA response, DMCM was more efficacious at alpha 1 beta 1 gamma 1 receptors and beta-CCM was more efficacious at alpha 2 beta 1 gamma 1 receptors. DMCM was inactive at alpha 3 beta 1 gamma 1 receptors, whereas beta-CCM was virtually inactive at alpha 5 beta 1 gamma 1 receptors. The benzodiazepine 4'-chlorodiazepam, which is a negative modulator resistent to flumazenil inhibition, acted at all the various GABAA receptors that contained a gamma subunit.

Allosteric Regulation↗
PubMed1991

Five type I modules of fibronectin form a functional unit that binds to fibroblasts and Staphylococcus aureus.

Fibronectin is a cell-adhesive protein comprised of three types of repeating homologous sequences, I, II, and III (Petersen, T.E., Thøgersen, H.C., Skorstengaard, K., Vibe-Pedersen, K., Sahl, P., Sottrup-Jensen, L., and Magnusson, S. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 137-141). The amino-terminal portion of fibronectin is comprised of five type I modules and mediates assembly of dimeric soluble fibronectin into insoluble fibrils by cultured fibroblasts, binding and cross-linking of fibronectin to Staphylococcus aureus, and binding and cross-linking of fibronectin to fibrin. It is not known whether these binding activities require individual type I modules, several modules, or all five modules. To answer this question, we generated recombinant truncated fibronectin molecules with deletions of or mutations in the amino-terminal type I modules. Binding to cellular fibronectin assembly sites and S. aureus required all five type I modules. In contrast, proteins with deletions of type I modules interacted well with fibrin.

Base Sequence↗
PubMed2006

[Modules biomass structure and growth pattern of Acanthopanax senticosus population in different habitats].

In this paper, a quantitative analysis was conducted on the functional modules' biomass structure and the relationships between biomass allocation and age of Acanthopanax senticosus population in three different habitats of coniferous and broad--leaved mixed forest, Quercus mongolica forest, and secondary miscellaneous forest. The results showed that the individual growth and modules' biomass accumulation of A. senticosus population were closely related to habitat conditions. The mean values of all functional modules' biomass under different ecological environments exhibited the same regularity, i. e. , stem modules > rhizome modules > leaf modules, and there were some similarities in the whole population of A. senticosus. The individual and each module's biomass of the population differed with the canopy density of forests, being larger in Q. mongolica forest with 40% of canopy density than in coniferous and broad-leaved mixed forest and secondary miscellaneous forest. The variations of ramet biomass allocation under different habit conditions indicated the important strategies in growth regulation and biomass allocation, i. e., more biomass was allocated to the leaves preferentially on small ramets, especially in the secondary miscellaneous forest with biggest canopy density, to ensure the full material product. There was the same regulation of heterogeneous speed growth in the relative weight increase of the leaves, stems and ramets of the population under the three habitat conditions.

Biomass↗
PubMed1991

Enhanced modulation of antibodies coating guinea pig leukemic cells in vitro and in vivo. The role of Fc gamma R expressing cells.

We have investigated the antigenic modulation induced by a number of antibody fragments and derivatives directed against the idiotype of the surface Ig of the L2C guinea pig B lymphoblastic leukemia, and studied the effects upon such modulation of the simultaneous presence of cells expressing Fc gamma receptors (FcR). In vitro studies confirmed previous work showing that antibody bivalency is required to induce modulation in vitro in simple systems. However, in the presence of isolated Kupffer cells, Fc-containing univalent antibodies were found to induce significant antigenic modulation, and the modulation induced by intact IgG was also found to be more rapid and extensive. Fragments that did not contain Fc regions behaved similarly in the presence or absence of Kupffer cells. Further investigations demonstrated that all three classes of human FcR can mediate modulation enhancement, and suggest that the mechanism involves indirect cross-linking of cell surface Ag via the antibody and effector cell FcR. In vivo studies showed that univalent antibody derivatives containing Fc regions did induce antigenic modulation, but that this was significantly reduced in comparison with bivalent antibodies, confirming their potential advantage for immunotherapy.

Animals↗
PubMed1990

Neuropeptide cotransmitters released from an identified cholinergic motor neuron modulate neuromuscular efficacy in Aplysia.

Intrinsic buccal muscle 5 (I5) in Aplysia is innervated by 2 motor neurons (termed B15 and B16). In addition to the classical transmitter ACh, B15 also contains the 2 neuropeptides SCPA and SCPB. In a previous study, we demonstrated that the SCPs were released from the terminals of B15 in the I5 muscle and that this release was sufficient to raise cAMP levels in I5 muscle fibers. Significant peptide release occurred only when B15 was stimulated at high frequency or at lower frequencies with a relatively long burst duration (Whim and Lloyd, 1989). In the present article, we examine the possibility that the SCPs released from B15 modulate I5 muscle contractions produced by stimulation of the second motor neuron, B16. Application of exogenous SCPs to I5 muscles increased the amplitude and relaxation rate of B16-evoked contractions. Stimulation of B15 using paradigms that have been shown previously to cause release of the SCPs resulted in a long-lasting increase in the amplitude and relaxation rate of muscle contractions evoked by B16. This modulation is unlikely to be due to the B15-induced muscle contractions themselves, because modulation of B16-evoked contraction amplitude and relaxation rate was observed when the contractions were blocked transiently by a cholinergic antagonist during B15 stimulation. Conversely, stimulation of B15 at frequencies that produce no measurable release of the SCPs did not elicit significant modulation of B16-evoked contractions. The minimum B15 stimulation frequency required to elevate muscle cAMP levels or to modulate B16-evoked contractions was found to be within the physiological range at which B15 fires during feeding. Therefore, the mechanism underlying the modulation of B16-evoked contractions by B15 is likely to involve the release of the SCPs from B15 terminals in the I5 muscle. With respect to behavior, this modulation of muscle contractions would be most likely to occur during food-induced arousal when both motor neurons fire at high frequency with brief interburst intervals.

Animals↗
PubMed1978

Chemical modification studies on the Ca2+-dependent protein modulator: the role of methionine residues in the activation of cyclic nucleotide phosphodiesterase.

Methionine residues have been implicated in the activation of cyclic nucleotide phosphodiesterase by the Ca2+-dependent protein modulator [Walsh, M., & Stevens, F.C. (1977) Biochemistry 16,2742-2749]. Treatment of the modulator with N-chlorosuccinimide in the presence of Ca2+ resulted in selective oxidation of methionine residues at positions 71,72, 76, and, possibly, 109 in the modulator sequence. These residues lie on the surface of the molecule exposed to solvent. This modification has several effects on the modulator protein: (1) the Ca2+-binding properties of the oxidized modulator are changed with apparent loss of high-affinity binding sites, (2) the oxidized protein no longer interacts with phosphodiesterase, and (3) troponin C like activities, viz., Ca2+-dependent change in mobility on urea-polyacrylamide gel electrophoresis and formation of a urea-stable complex with troponin I, are lost upon oxidation of the modulator. The phosphodiesterase binding domain of the modulator protein appears to be located between the second and third Ca2+-binding loops, a region of the molecule known from previous partial proteolysis studies [Walsh, M., Stevens, F.C., Kuznicki, J., & Drabikowski, W.(1977), J. Biol. Chem. 252, 7440-7443] to be exposed in the presence of Ca2+.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Modulation transfer functions: a comparison of the results of three methods.

Modulation transfer functions (MTFs) were measured with three different psychoacoustical paradigms in the same normal-hearing subjects. In the temporal-probe method, the threshold of a 4-ms probe tone (frequencies of 1000 and 4000 Hz) was measured at various envelope phases within a 100% sinusoidally amplitude-modulated (SAM) noise at modulation frequencies from 2 to 256 Hz. For the derived-MTF method, the threshold of a 500-ms tone at 1000 and 4000 Hz was measured in the same noise at the same modulation frequencies. For the modulation-detection paradigm, modulation thresholds were measured as a function of modulation frequency for bandpass filtered SAM noise centered at 1000 and 4000 Hz. MTFs with lowpass shapes were observed with all three methods. Differences were observed in the cutoff frequencies and/or attenuation rates when the data were fitted with lowpass filter transfer functions. Factors influencing those differences are discussed.

Adult↗
PubMed1989

Expression of types I and IV collagen genes in normal and in modulated corneal endothelial cells.

Expression of type I and type IV collagen genes was studied in normal endothelial cells and in modulated endothelial cells (formerly designated as fibroblastic corneal endothelial cells: FCEC). There appear to be distinct collagen phenotypes in these cells; normal cells produce type IV collagen as a major type, while the modulated cells produce predominantly type I collagen. The absence of type I synthesis in normal cells, and absence of type IV collagen in FCEC were confirmed by immunoblot analysis of the accumulated collagen in the cellular and medium layers in cultures of these cells. When collagen mRNAs were translated in a cell-free system, the results indicate that neither type I collagen RNAs in the normal cells, nor type IV collagen RNAs in the modulated cells were translated. Using cloned cDNA probes, the relative quantities of transcripts of these collagens were determined by slot blot hybridization; normal cells, which synthesize no detectable type I collagen, were found to contain type I collagen RNAs in similar amounts as did the modulated cells, while the levels of type IV RNAs in modulated cells were as high as those in normal cells, in spite of the absence of their translational products. Northern blot analysis demonstrated that there are no distinct differences in the size of type I collagen RNAs in the normal and modulated cells. In contrast, type IV collagen RNA in the modulated cells was much smaller than the normal cells, suggesting that the alpha 1(IV) RNA is readily degraded.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Selective modulation of two human monocyte Fc receptors for IgG by immobilized immune complexes.

Two types of IgG FcR, FcRI and FcRII, are constitutively expressed by human monocytes. FcRI (identified by mAb 32.2) binds human (h) IgG, FcRII (identified by mAb IV.3) has a low affinity for hIgG but interacts strongly with murine (m) IgG1. These receptors can be assayed by using indicator E sensitized by hIgG (EA-hIgG) or mIgG1 (EA-mIgG1), respectively. We further characterized these two FcR by modulation studies by using substrate-immobilized immune complexes containing rabbit IgG, goat IgG, or one of the mouse Ig classes or subclasses. After incubating monocytes in microtiter wells containing such immune complexes, binding of the two types of indicator red cells on the apical surface of the monocytes was quantitated using a photometric assay employing the pseudoperoxidase activity of E. No effect on the binding of sensitized E was observed after incubation of monocytes with immune complexes containing mouse IgE, IgA, or IgM, or F(ab')2 fragments of rabbit IgG. High concentrations of immune complexes containing IgG of mouse, rabbit, or goat, however, were able to induce a decrease in binding of both types of sensitized E, suggestive of modulation of both FcRI and FcRII. At lower concentrations of immune complexes, more selective patterns of modulation emerged. Under these conditions, immune complexes containing mIgG1 or mIgG2b, or, surprisingly, goat IgG induced a selective decrease in the binding of EA-mIgG1 (FcRII modulation), while immune complexes containing mIgG2a or rabbit IgG mainly affected the binding of EA-hIgG (FcRI modulation). By using anti-FcR mAb IV.3, it was confirmed that FcRII was modulated from the apical surface of monocytes after incubation on immune complex coated substrates. Selectivity of FcR-modulation was demonstrated by showing that under these conditions binding of anti-C receptor mAb, and several other anti-monocyte mAb did not decrease.

Antibodies, Monoclonal↗
PubMed1986

Effect of T3 modulation on pokeweed mitogen-induced T cell activation: evidence for an alternative pathway of T cell activation.

Modulation of the T3 molecule on human T cells with monoclonal anti-T3 antibodies has been shown to result in the disappearance of the T3-Ti complex from the membrane and to preclude subsequent T cell activation by various mitogenic and antigenic stimuli. We have examined the effect of T3 modulation on pokeweed mitogen (PWM)-induced T cell activation. T3 modulation was accomplished by incubating peripheral blood mononuclear cells (PBMC) or mixtures of T cells and non-T cells at 37 degrees C for 18 hr in the presence of UCHT-1, a mouse IgG1 anti-T3 monoclonal antibody. Only donors whose PBMC were unresponsive to the mitogenic activity of this antibody were selected. Although T3 modulation resulted in complete to substantial inhibition of T cell proliferation induced by low PWM concentrations of 5 or 50 ng/ml, it had no effect on T cell proliferation when PWM was added at a concentration of 0.5 and 5 micrograms/ml. The results demonstrate that the higher doses of PWM can induce T cell proliferation via an alternative pathway that does not involve participation of the T3-Ti complex. In contrast, irrespective of the PWM dose added, T3 modulation almost totally inhibited PWM-induced interleukin 2 (IL 2) production. The differential effect of T3 modulation on IL 2 production and on T cell proliferation induced by high doses of PWM suggests that this alternative pathway of T cell proliferation is IL 2 independent. This suggestion was additionally substantiated by the lack of effect of anti-Tac, and anti-IL 2 receptor antibody, on PWM-induced proliferation of T3-modulated T cells. In conclusion our data demonstrate that high doses of PWM can induce T cells to proliferate via an alternative pathway that does not involve perturbation of the T3-Ti complex.

Adult↗