Interaction of cationic ultrasmall superparamagnetic iron oxide nanoparticles with human melanoma cells.

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) are currently under development for the intracellular delivery of therapeutics. However, the mechanisms of cellular uptake and the cellular reaction to this uptake, independent of therapeutics, are not well defined. The interactions of biocompatible cationic aminoUSPIONs with human cells was studied in 2D and 3D cultures using biochemical and electron microscopy techniques. AminoUSPIONs were internalized by human melanoma cells in 2D and 3D cultures. Uptake was clathrin mediated and the particles localized in lysosomes, inducing activation of the lysosomal cathepsin D and decreasing the expression of the transferrin receptor in human melanoma cells and/or skin fibroblasts. AminoUSPIONs deeply invaded 3D spheroids of human melanoma cells. Thus, aminoUSPIONs can invade tumors and their uptake by human cells induces cell reaction.

Characterization of an interaction between fetal hemoglobin and lipid A of LPS resulting in augmented induction of cytokine production in vivo and in vitro.

A previously described extract of sheep fetal liver was reported to reverse many of the cytokine changes associated with aging in mice, including an augmented spleen cell ConA-stimulated production of IL-4 and decreased production of IL-2. Similar effects were not seen with adult liver preparations. These changes were observed in various strains of mice, including BALB/c, DBA/2 and C57BL/6, using mice with ages ranging from 8 to 110 weeks. Preliminary characterization of this crude extract showed evidence for the presence of Hb gamma chain, as well as of lipid A of LPS. We show below that purified preparations of sheep fetal Hb, but not adult Hb, in concert with suboptimally stimulating doses of LPS (lipid A), cooperate in the regulation of production of a number of cytokines, including TNFalpha and IL-6, in vitro. Furthermore, isolated fresh spleen or peritoneal cells from animals treated in vivo with the same combination of Hb and LPS, showed an augmented capacity to produce these cytokines on further culture in vitro. Evidence was also obtained for a further interaction between CLP, LPS and fetal Hb itself in this augmented cytokine production. These data suggest that some of the functional activities in the fetal liver extract reported earlier can be explained in terms of a novel immunomodulatory role of a mixture of LPS (lipid A) and fetal Hb.

Aalenian to Cenomanian Radiolaria of the Bermeja Complex (Puerto Rico) and Pacific origin of radiolarites on the Caribbean Plate

The study of the radiolarian ribbon chert is a key in determining the origins of associated Mesozoic oceanic terranes and may help to achieve a general agreement regarding the basic principles on the evolution of the Caribbean Plate. The Bermeja Complex of Puerto Rico, which contains serpentinized peridotite, altered basalt, amphibolite, and chert (Mariquita Chert Formation), is one of these crucial oceanic terranes. The radiolarian biochronology presented in this work is mainly based by correlation on the biozonations of Baumgartner et al. (1995) and O'Dogherty (1994) and indicates an early Middle Jurassic to early Late Cretaceous (late Bajocian-early Callovian to late early Albian-early middle Cenomanian) age. The illustrated assemblages contain about 120 species, of which one is new (Pantanellium karinae), and belonging to about 50 genera. A review of the previous radiolarian published works on the Mariquita Chert Formation and the results of this study suggest that this formation ranges in age from Middle Jurassic to early Late Cretaceous (late Aalenian to early-middle Cenomanian) and also reveal a possible feature of the Bermeja Complex, which is the younging of radiolarian cherts from north to south, evoking a polarity of accretion. On the basis of a currently exhaustive inventory of the radiolarite facies s.s. on the Caribbean Plate, a re-examination of the regional distribution of Middle Jurassic sediments associated with oceanic crust, and a paleoceanographic argumentation on the water currents, we come to the conclusion that the radiolarite and associated Mesozoic oceanic terranes of the Caribbean Plate are of Pacific origin. Eventually, a discussion on the origin of the cherts of the Mariquita Formation illustrated by Middle Jurassic to middle Cretaceous geodynamic models of the Pacific and Caribbean realms bring up the possibility that the rocks of the Bermeja Complex are remnants of two different oceans.

Interaction of Fas(Apo-1/CD95) with proteins implicated in the ubiquitination pathway.

Fas(Apo-1/CD95), a receptor belonging to the tumor necrosis factor receptor family, induces apoptosis when triggered by Fas ligand. Upon its activation, the cytoplasmic domain of Fas binds several proteins which transmit the death signal. We used the yeast two-hybrid screen to isolate Fas-associated proteins. Here we report that the ubiquitin-conjugating enzyme UBC9 binds to Fas at the interface between the death domain and the membrane-proximal region of Fas. This interaction is also seen in vivo. UBC9 transiently expressed in HeLa cells bound to the co-expressed cytoplasmic segment of Fas. FAF1, a Fas-associated protein that potentiates apoptosis (Chu et al. (1996) Proc. Natl. Acad. Sci. USA 92, 11894-11898), was found to contain sequences similar to ubiquitin. These results suggest that proteins related to the ubiquitination pathway may modulate the Fas signaling pathway.

Probable metabolic interaction between methadone and fluvoxamine in addict patients.

We report five cases where fluvoxamine (FLVX) was added to maintenance treatment with methadone (MTD) in addict patients with affective disorders. In view of the implication of FLVX in several metabolic drug interactions, MTD plasma levels were measured before and after treatment with FLVX. A slight increase (approximately 20% of the MTD plasma level/dose ratio) occurred in two cases. In the remaining three patients, the interaction was more pronounced (40-100% increase of the MTD plasma level/dose ratio), with clinical manifestations of opiate withdrawal after stopping FLVX therapy in one case. Caution is needed when starting or stopping treatment with FLVX in patients receiving maintenance treatment with methadone.

Interaction of antigenic peptides with MHC class I molecules on living cells studied by photoaffinity labeling.

Using a direct binding assay based on photoaffinity labeling, we have studied the interaction of antigenic peptides with murine MHC class I molecules on living cells. Photoreactive derivatives were prepared by N-terminal amidation with iodo, 4-azido salicylic acid of the Kd restricted Plasmodium berghei circumsporozoite (P.b. CS) peptide 253-260 (YIPSAEKI) and the Db-restricted Adenovirus 5 early region 1A (Ad5 E1A) peptide 234-243 (SGPSNTPPEI). As assessed in functional competition experiments, both peptide derivatives retained the specific binding activity of the parental peptides for Kd or Dd, respectively. The P.b. CS photoprobe specifically labeled Kd molecules on P815 (H-2d) cells, but failed to label RMA (H-2b) cells. Conversely, the Ad5 E1A photoprobe specifically labeled Db molecules on RMA cells, but failed to label P815 cells. When the two photoprobes were tested on a panel of Con A-activated spleen cells expressing 10 different H-2 haplotypes, significant photoaffinity labeling was observed only on H-2d cells with the P.b. CS photoprobe and on H-2b cells with the Ad5 E1A photoprobe. Labeling of cell-associated Kd or Db molecules with the photoprobes was specifically inhibited by antigenic peptides known to be presented by the same class I molecule. Photoaffinity labeling of Kd with the P.b. CS photoprobe was used to study the dynamics of peptide binding on living P815 cells. Binding increased steadily with the incubation period (up to 8 h) at 37 degrees C and at ambient temperature, but was greatly reduced (greater than 95%) at 0 to 4 degrees C or in the presence of ATP synthesis inhibitors. The magnitude of the labeling was twofold higher at room temperature than at 37 degrees C. In contrast, binding to isolated Kd molecules in solution rapidly reached maximal binding, particularly at 37 degrees C. Dissociation of the photoprobe from either cell-associated or soluble Kd molecules was similar, with a half time of approximately 1 h at 37 degrees C, whereas the complexes were long-lived at 4 degrees C in both instances.

A positive interaction between inhibitors of protein synthesis and cefepime in the fight against methicillin-resistant Staphylococcus aureus.

Quinupristin-dalfopristin (Q-D) synergizes with cefepime for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Here, we studied whether the synergism was restricted to MRSA and if it extended to non-beta-lactam cell wall inhibitors or to other inhibitors of protein synthesis. Three MRSA and two methicillin-susceptible S. aureus (MSSA) strains were tested, including an isogenic pair of mecA (-)/mecA (+) S. aureus Newman. The drug interactions were determined by fractional inhibitory concentration (FIC) indices and population analysis profiles. The antibacterial drugs that we used included beta-lactam (cefepime) and non-beta-lactam cell wall inhibitors (D-cycloserine, fosfomycin, vancomycin, teicoplanin), inhibitors of protein synthesis (Q-D, erythromycin, chloramphenicol, tetracycline, linezolid, fusidic acid), and polynucleotide inhibitors (cotrimoxazole, ciprofloxacin). The addition of each protein inhibitor to cefepime was synergistic (FIC ≤ 0.5) or additive (FIC > 0.5 but < 1) against MRSA, but mostly indifferent against MSSA (FIC ≥ 1 but ≤ 4). This segregation was not observed after adding cotrimoxazole or ciprofloxacin to cefepime. Population analysis profiles were performed on plates in the presence of increasing concentrations of the cell wall inhibitors plus 0.25 × minimum inhibitory concentration (MIC) of Q-D. Cefepime combined with Q-D was synergistic against MRSA, but D-cycloserine and glycopeptides were not. Thus, the synergism was specific to beta-lactam antibiotics. Moreover, the synergism was not lost against fem mutants, indicating that it acted at another level. The restriction of the beneficial effect to MRSA suggests that the functionality of penicillin-binding protein 2A (PBP2A) was affected, either directly or indirectly. Further studies are necessary in order to provide a mechanism for this positive interaction.

Petrology and chemistry of the Chalten Plutonic Complex and implications on the magmatic and tectonic evolution of the Southernmost Andes (Patagonia) during the Miocene

Résumé Scientific:Pétrologie et Géochimie du Complexe Plutonique de Chaltén et les conséquences pour l'évolution magmatique et tectonique du Andes du Sud (Patagonia) pendant le MiocèneLe sujet de cette thèse est le Complexe Plutonique de Chaltén (CHPC), situé à la frontière entre le Chili et l'Argentine, en Patagonie (49°15'S). Ce complexe s'est mis en place au début du Miocène, dans un contexte de changements tectoniques importants. La géométrie et la vitesse de migration des plaques en Patagonie a été modifiée suite l'ouverture de la plaque Farallon il y a 25Ma (Pardo-Casas and Molnar 1987) et la subduction de la ride active du Chili sous la plaque sud-américaine il y a 14Ma (Cande and Leslie 1986). Les effets de cette reconfiguration tectonique sur la morphologie et le magmatisme de la plaque supérieure sont encore sujets à discussion. Dans ce contexte, un groupe d'intrusions miocènes - telle que le CHPC - est particulièrement intriguant, car en position transitionnelle entre le batholithe patagonien et l'arc volcanique cénozoïque et récent à l'ouest, et les laves de plateau de Patagonie à l'est (Fig. 1). A cause de leur position tectonique transitoire, ces plutons isolés hors du batholithe représentent un endroit clé pour comprendre les interactions entre la tectonique à large échelle et le magmatisme en Patagonie. Ici, je présente de nouvelles données de terrain, petrologiques, géochimiques et géochronologiques dans le but de caractériser la nature du CHPC, qui était largement inconnu avant cette étude, dans le but de tester l'hypothèse de migration de l'arc et erosion par subduction.Les résultats de l'investigation géochimique (chapitre 2) montrent que le CHPC n'est qu'un exemple parmi les plutons isolés d'arrière arc ave une composition calco-alcaline caractéristique, c-à-d une signature d'arc. La plupart de ces plutons isolés ont une composition alcaline. Le CHPC, contrairement, a une signature calco-alcaline avec Κ intermédiaire, tel que le batholithe patagonien et la plupart des roches volcaniques quaternaires liées à l'arc le long des Andes.De nouvelles données géochronologiques U-Pb de haute précision sur des zircons, acquis par TIMS, sur le CHPC donnent des âges entre 17.0 et 16.4Ma. Les âges absolus sont en accord avec la séquence intrusive déduite des relations de terrain (chapitre 1). Ces données sont les premières contraintes d'âge U-Pb sur le CHPC. Elles montrent clairement que l'histoire magmatique du CHPC n'a pas de lien direct avec la subduction de la ride à cette latitude (Cande and Leslie 1986), car le complexe est au moins 6Ma plus ancien.Une comparaison en profondeur avec les autres intrusions d'âge Miocène en Patagonie révèlent - pour la première fois - une évolution temporelle intéressante. Il y a une tendance E-W distincte au magmatisme calco-alcalin entre 20-16Ma avec une diminution de l'âge vers l'est - le CHPC est l'expression la plus orientale de cette tendance. Je suggère que la relation espace-temps reflète une migration vers l'est (vers le continent) de l'arc magmatique. Je propose que le facteur principal contrôlant cette migration est la subduction rapide suite à la reconfiguration de la vitesse des plaques tectoniques après l'ouverture la plaque Farallon (à ~26Ma) qui résulterait en une déformation importante ainsi qu'à des taux élevés d'érosion dans la fosse de subduction.Les rapports d'isotopes radiogéniques (Pb, Sr, Nd) élevés, une signature 6018 basse et un rapport Th/La élevé sont des paramètres distinctifs pour les roches mafiques du CHPC. Le modèle isotopique présenté (chapitre 2) suggère que cette signature reflète une contamination de la source, dans le coin de manteau, plutôt qu'une contamination crustale. La signature des éléments en trace du CHPC indiquent que le coin de manteau a été contaminé par des composés terrigènes, le plus vraisemblablement par des sédiments paléozoïques.Les travaux de terrain, la pétrographie et la géothermobarométrie ont été utilisés dans le but de comprendre l'histoire interne du CHPC (chapitre 3). Ces données suggèrent deux niveaux distincts de cristallisation : l'un dans la croûte moyenne (6 à 4.5kbar) et l'autre à un niveau peu profond (3.5 à 2kbar). La modélisation isotopique AFC de la contamination crustale indique des taux variables d'assimilation, qui ne sont pas corrélés avec le degré de différenciation. Cela suggère que différents volumes de magma se sont différenciés en profondeur, de façon indépendante. Cela implique que le CHPC se serait formés en plusieurs puises de magmas provenant d'au moins trois sources différentes. Les textures des granodiorites et des granites indiquent des teneurs élevées en cristaux avant la mise en place et, par conséquent, des températures d'emplacement faibles. Les observations de terrain montrent que les roches mafiques sont déformées, alors que ce n'est pas le cas pour les granodiorites et granites (plus jeunes). La déformation des roches mafiques est encore sujet de recherche, afin de savoir si elle est liée à la déformation régionale en régime compressif ou à l'emplacement lui-même. Cependant, la mise en place de grand volume de magma felsique riche en cristaux suggère un régime d'extension.Scientific Abstract:Petrology and chemistry of the Chaltén Plutonic Complex and implications on the magmatic and tectonic evolution of the Southernmost Andes (Patagonia) during the MioceneThe subject of this thesis is the Chaltén Plutonic Complex (CHPC) located at the frontier between Chile and Argentina in Patagonia (at 49° 15 'Southern latitude). This complex intruded during early Miocene in a context of major tectonics changes. The plate geometry of Patagonia has been modified by changes in the plate motions after the break up of the Farallôn plate at 25Ma (Pardo-Casas and Molnar 1987) and by the subduction of the Chile spreading Ridge beneath South-America at 14 Ma (Cande and Leslie 1986). The effects of this tectonic setting on the morphology and the magmatism of the overriding plate are a matter of on-going discussion. Particularly intriguing in this context is a group of isolated Miocene intrusions - like the CHPC - which are located in a transitional position between the Patagonian Batholith and the Cenozoic and Recent volcanic arc in the West, and the Patagonian plateau lavas in the East (Fig. 1). Due to their transient tectonic position these isolated plutons outside the batholith represent a key to understanding the interaction between global-scale tectonics and magmatism in Patagonia. Here, I present new field, penological, geochemical and geochronological data to characterize the nature of the CHPC, which was largely unknown before this study, in order to test the hypothesis of time- transgressive magmatism.The results of the geochemical investigation (Chapter 2) show that the CHPC is only one among these isolated back-arc plutons with a characteristic calc-alkaline composition, i.e. arc signature. Most of these isolated intrusives have an alkaline character. The CHPC, in contrast, has a medium Κ calc-alkaline signature, like the Patagonian batholith and most of the Quaternary arc-related volcanic rocks along the Andes.New high precision TIMS U-Pb zircon dating of the CHPC yield ages between 17.0 to 16.4 Ma. The absolute ages support the sequence of intrusion relations established in the field (Chapter 1). These data are the first U-Pb age constraints on the CHPC, and clearly show that the magmatic history of CHPC has no direct link to the subduction of the ridge, since this complex is at least 6 Ma older than the time of collision of the Chile ridge at this latitude (Cande and Leslie 1986).An in-depth comparison with other intrusion of Miocene age in Patagonia reveals - for the first time - an interesting temporal pattern. There is a distinct E-W trend of calc-alkaline magmatism between 20-16 Ma with the younging of ages in the East - the CHPC is the easternmost expression of this trend. I suggest that this time-space relation reflects an eastward (landward) migration of the magmatic arc. I propose that main factor controlling this migration is the fast rates of subduction after the major reconfigurations of the plate tectonic motions after the break up of the Farallôn Plate (at -26 ) resulting in strong deformation and high rates of subduction erosion.High radiogenic isotope ratios (Pb, Sr, Nd) ratios, low 5018 signature and high Th/La ratios in mafic rocks are distinctive features of the CHPC. The presented isotopic models (Chapter 2) suggest that this signature reflects source contamination of the mantle wedge rather than crustal contamination. The trace element signature of the CHPC indicates that the mantle wedge was contaminated with a terrigenous component, most likely from Paleozoic sediments.Fieldwork, petrography and geothermobarometry were used to further unravel the internal history of the CHPC (Chapter 3). These data suggest two main levels of crystallization: one a mid crustal levels (6 to 4.5 kbar) and other a shallow level (3.5 to 2 kbar). Isotopic AFC modeling of crustal contamination indicate variable rates of assimilation, which are not correlated with the degree of differentiation. This suggests that different batches of magma differentiate independently at depths. This implies that the CHPC would have formed by several pulses of magmas from at least 3 different sources. Textures of granodiorites and granites indicate a high content of crystals previous to the emplacement and consequently low emplacement temperatures. Field observations show that the mafic rocks are deformed, whereas the (younger) granodiorites and granites are not. It is still subject of investigation whether the deformation of the mafic rocks is related to regional deformation during a compressional regime or to the emplacement it self. However, the emplacement of huge amount of crystal rich felsic magmas suggests an extensional regime.Résumé Grand PublicPétrologie et Géochimie du Complexe Plutonique de Chaltén et les conséquences pour l'évolution magmatique et tectonique du Andes du Sud (Patagonia) pendant le MiocèneLe Complexe Plutonique de Chaltén (CHPC) est un massif montagneux situé à 49°S à la frontière entre le Chili et l'Argentine, en Patagonie (région la plus au sud de l'Amérique du Sud). Il est composé de montagnes qui peuvent atteindre plus de 3000 mètres d'altitude, telles que le Cerro Fitz Roy (3400m) et le Cerro Torre (3100m). Ces montagnes sont composées de roches plutoniques, c.-à-d. des magmas qui se sont refroidis et ont cristallisés sous la surface terrestre.La composition chimique de ces roches montre que les magmas, qui ont formé ce complexe plutonique, font partie d'un volcanisme d'arc. Celui-ci se forme lorsqu'une plaque océanique plonge sous une plaque continentale. Les géologues appellent ce processus « subduction ». Dans un tel scénario, le manteau terrestre, qui se fait prendre entre ces deux plaques, fond pour former ainsi du magma. Ce magma remonte à travers la plaque continentale vers la surface. Si celui-ci atteint la surface, il forme les roches volcaniques, comme par exemple des laves. S'il n'atteint pas la surface, le magma se refroidit pour former finalement les roches plutoniques.Le long de la marge ouest d'Amérique du Sud, la plaque Nazca - qui se situe au sud-est de la plaque océanique pacifique - passe en dessous de la plaque d'Amérique du Sud. La bordure ouest du sud de la plaque sud-américaine a également été affectée par d'autres processus tectoniques, tels que des changements dramatiques dans les déplacements de plaques (il y a 25Ma) et la collision de la ride du Chili (depuis 15 Ma jusqu'à aujourd'hui). Ces caractéristiques tectoniques et magmatiques font de cette région un haut lieu pour les géologues. La plaque Nazca, s'est formée suite à l'ouverture d'une plaque océanique plus ancienne, il y a 25Ma. Cette ouverture est liée aux vitesses de subduction les plus rapides jamais connues. La ride du Chili est l'endroit où le sol de l'Océan Pacifique s'ouvre, formant deux plaques océaniques : les plaques Nazca et Antarctique. La ride du Chili subducte sous la plaque sud-américaine depuis 15Ma, en association avec la formation de grands volumes de magma ainsi que des changements morphologiques importants. La question de savoir lequel de ces changements tectoniques globaux affecte la géologie et la géographie de Patagonie a été, et est encore, discutée pendant de nombreuses années. De nombreux chercheurs suggèrent que la plupart des caractéristiques morphologiques et magmatiques en Patagonie sont liés à la subduction de la ride du Chili, mais cette suggestion est encore débattue comme le montre notre étude.Le batholithe de Patagonie du sud (SPB) est un énorme massif composé de roches plutoniques et il s'étend tout au long de la côte ouest de Patagonie (au sud de 47°S). Ces roches correspondent certainement aux racines d'un ancien arc volcanique, qui a été soulevé et érodé. Le CHPC, ainsi que d'autres petites intrusions dans la région, se situe dans une position exotique, à 100km à l'est du SPB. Certains chercheurs suggèrent que ces intrusions pourraient être liées à la subduction de la ride du Chili.Afin de débattre de cette problématique, nous avons utilisé différentes méthodes géochronologiques pour déterminer l'âge du CHPC et le comparer (a) à l'âge des roches intrusives similaires du SPB et (b) à l'âge de la collision de la ride du Chili. Dans ce travail, nous prouvons que le CHPC s'est formé au moins 7Ma avant la collision avec la ride du Chili. Sur la base des âges du CHPC et de la composition chimique de ses roches et minéraux, nous proposons que le CHPC fait partie d'un arc volcanique ancien. La migration de l'arc volcanique plus profondément dans le continent résulte de la grande vitesse de subduction entre 25 et lOMa. Des caractéristiques évidentes pour un tel processus - telles qu'une déformation importante et une vitesse d'érosion élevée - peuvent être rencontrées tout au long de la bordure ouest de l'Amérique du sud.

The Carboniferous Baralacha La basaltic dykes (Upper Lahul, Ladakh): remnants of an early rifting event along the Indian northern plate

The Lower Carboniferous Baralacha La basaltic dykes were emplaced along transtensional faults. The basalts exhibit tholeiitic and alkaline affinities. The tholeiites are TiO2-poor, moderately enriched in light rare earth (LREE), and display Nb and Ta negative and Th positive anomalies. The alkali basalts, compared to the tholeiites, have higher TiO2, rare earth and highly incompatible trace element contents and greater LREE enrichments. The Nd and Pb isotope compositions of the Baralacha La basalts suggest that they derive from the partial melting of an enriched OIB mantle source. characterized by a HIMU component, and contaminated by the lower continental crust. The Baralacha La dyke swarm represent the remnants of an early rifting event on the northern Indian passive margin.

Phosphate and zinc transport and signalling in plants: toward a better understanding of their homeostasis interaction.

Inorganic phosphate (Pi) and zinc (Zn) are two essential nutrients for plant growth. In soils, these two minerals are either present in low amounts or are poorly available to plants. Consequently, worldwide agriculture has become dependent on external sources of Pi and Zn fertilizers to increase crop yields. However, this strategy is neither economically nor ecologically sustainable in the long term, particularly for Pi, which is a non-renewable resource. To date, research has emphasized the analysis of mineral nutrition considering each nutrient individually, and showed that Pi and Zn homeostasis is highly regulated in a complex process. Interestingly, numerous observations point to an unexpected interconnection between the homeostasis of the two nutrients. Nevertheless, despite their fundamental importance, the molecular bases and biological significance of these interactions remain largely unknown. Such interconnections can account for shortcomings of current agronomic models that typically focus on improving the assimilation of individual elements. Here, current knowledge on the regulation of the transport and signalling of Pi and Zn individually is reviewed, and then insights are provided on the recent progress made towards a better understanding of the Zn-Pi homeostasis interaction in plants.

Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity.

As an approved vaccine adjuvant for use in humans, alum has vast health implications, but, as it is a crystal, questions remain regarding its mechanism. Furthermore, little is known about the target cells, receptors, and signaling pathways engaged by alum. Here we report that, independent of inflammasome and membrane proteins, alum binds dendritic cell (DC) plasma membrane lipids with substantial force. Subsequent lipid sorting activates an abortive phagocytic response that leads to antigen uptake. Such activated DCs, without further association with alum, show high affinity and stable binding with CD4(+) T cells via the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1). We propose that alum triggers DC responses by altering membrane lipid structures. This study therefore suggests an unexpected mechanism for how this crystalline structure interacts with the immune system and how the DC plasma membrane may behave as a general sensor for solid structures.