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Continuous release of interleukin-2 from liposomal IL-2 (mixture of interleukin-2 and liposomes) after subcutaneous administration to mice.

Recombinant interleukin-2 (IL-2) was strongly and almost completely adsorbed onto small and hydrophobic liposomes by simple mixing under optimal conditions (liposome: DSPC-DSPG; molar ratio, 10:1; 30-50 nm in size, ratio of IL-2 to liposome: 4.0 JRU/nmol lipid). This liposomal IL-2 displayed better distribution after intravenous administration in mice and improved therapeutic effect against experimental M5076 metastases, as reported previously. In this study, the elimination of IL-2 from the dosing area was investigated when the liposomal IL-2 was administered to mice subcutaneously. The results suggest that the release of IL-2 from this liposome was continuous and almost complete. The mean residence time (MRT) of IL-2 in the dosing area was 11.0 +/- 1.65 hr. This resulted in the 8-fold times enhancement of MRT in the systemic circulation by the presence of liposomes, and IL-2 was detected in the serum for 2 days. Using this liposomal IL-2 is expected to have the potential to decrease the number of injections and enhance the efficacy of IL-2 in immunotherapies and therapies against tumor.

Adsorption↗

Enhancement of human immunodeficiency virus type 1 infection by cationic liposomes: the role of CD4, serum and liposome-cell interactions.

We have reported previously the enhancement of the infectivity of human immunodeficiency virus type 1 (HIV-1) by liposomes composed of the cationic lipid N-[2,3-(dioleyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTMA). To determine the mechanism by which this process occurs, we have investigated the role of CD4, serum concentration and liposome-cell interactions in the DOTMA-mediated stimulation of HIV-1 infection of A3.01 cells. Serum alone significantly inhibited the binding and infectivity of HIV-1, but DOTMA-mediated enhancement of infectivity was more pronounced in the presence of serum than in its absence. HIV-1 binding to cells was increased in the presence of DOTMA liposomes, DEAE-dextran and polybrene, all of which also enhanced infectivity to a similar extent at comparable concentrations. Fluorescence dequenching measurements indicated that DOTMA liposomes fused with HIV-1, but not with cell membranes, in the presence of serum. The enhancing effect of DOTMA liposomes on HIV-1 infectivity was CD4-dependent, and appeared to involve virus-liposome fusion and liposome binding to the cell surface. DOTMA liposomes did not mediate infection of the CD4-K562 and Raji cell lines.

Antibodies, Monoclonal↗

Improved therapeutic responses in a xenograft model of human B lymphoma (Namalwa) for liposomal vincristine versus liposomal doxorubicin targeted via anti-CD19 IgG2a or Fab' fragments.

PURPOSE: Monoclonal antibody-mediated targeting of liposomal anticancer drugs to surface antigens expressed on malignant B cells can be an effective strategy for treating B-cell malignancies. In a murine model of human B-cell lymphoma, we have made in vitro and in vivo comparisons of long-circulating sterically stabilized (Stealth) immunoliposome (SIL) formulations of two anticancer drugs, vincristine (VCR) and doxorubicin (DXR), with different mechanisms of action and drug release rates. EXPERIMENTAL DESIGN: SIL formulations of VCR or DXR were conjugated to the monoclonal antibody anti-CD19 (SIL[alphaCD19]) or its Fab' fragments (SIL[Fab']). Specific binding of SILs to Namalwa cells was studied using radiolabeled liposomes, and cytotoxicities of DXR- or VCR-loaded SILs were quantitated by a tetrazolium assay. Pharmacokinetic and drug leakage experiments were performed in mice using dual-labeled liposomes, and the therapeutic responses of SILs were evaluated in a Namalwa (human B lymphoma) cell xenograft model. RESULTS: SIL[alphaCD19] or SIL[Fab'] had higher association with and cytotoxicity against Namalwa cells than nontargeted liposomes. SIL[Fab'] had longer circulation times than SIL[alphaCD19], and VCR had faster release rates from the liposomes than DXR. SIL formulations of either VCR or DXR had significantly better therapeutic outcomes than nontargeted liposomes or free drugs. SILs loaded with VCR were superior to those loaded with DXR. SIL[Fab'] had better therapeutic outcomes than SIL[alphaCD19] for the drug DXR but were equally efficacious for the drug VCR. CONCLUSIONS: Treatment of a B lymphoma model with single injections of anti-CD19-targeted liposomal formulations of VCR resulted in high levels of response and long-term survivors. Responses to anti-CD19-targeted liposomal DXR were more modest, although the longer circulation times of SIL[Fab'] versus SIL[alphaCD19] led to superior therapeutics for DXR-loaded immunoliposomes.

Animals↗

Enhancement of anti-metastatic activity of pentoxifylline by encapsulation in conventional liposomes and sterically stabilized liposomes in murine experimental B16F10 melanoma model.

Pentoxifylline has been shown to exhibit anti-metastatic activity by inhibiting homing of B16F10 melanoma cells in the murine experimental metastasis model. In this study, the effect of encapsulation of pentoxifylline in conventional and sterically stabilized liposomes on its anti-metastatic activity in the murine experimental metastasis model was investigated. After a single intravenous dose (10, 20 or 40 mg kg(-1)), pentoxifylline solution, as well as conventional pentoxifylline liposomes, significantly reduced the number of pulmonary nodules compared with the untreated control group. Conventional pentoxifylline liposomes showed significantly higher inhibition (69%) of pulmonary tumour nodule formation at a dose of 20mg kg(-1) as compared with pentoxifylline solution (49%) at the same dose. Encapsulation of pentoxifylline in sterically stabilized liposomes prepared by incorporation of monomethoxypolyethyleneglycol (5000)-cholesteryl ester further enhanced the inhibition of pulmonary nodule formation (77%) at a dose of 20 mg kg(-1) as compared with conventional pentoxifylline liposomes. Overall, the results suggest that encapsulation of pentoxifylline in conventional liposomes enhanced its anti-metastatic activity. Steric stabilization of pentoxifylline liposomes also resulted in a two-fold increase in anti-metastatic activity (at dose of 10 mg kg(-1)) as compared with conventional liposomes.

Animals↗

Preparation and characterization of echogenic liposome as an ultrasound contrast agent: size-dependency and stabilizing effect of cholesterol on the echogenicity of gas-entrapping liposome.

The liposome entrapping CO2 gas inside the vesicle, which is called the echogenic liposome, has been made and characterized in vitro as an ultrasound contrast agent. The small unilamellar vesicle (SUV), large unilamellar vesicle (LUV) and multilamellar vesicle (MLV) as echogenic liposomes were compared in their echogenic efficiency and stability, and the effect of size and acoustic property was tested. The acoustic reflectivity increased with the increase in size of the vesicle, largest for the gas filled MLV among the three liposome suspensions. The acoustic reflectivity obtained with the echogenic MLV was larger than that of the gas bubbles enclosed within a surfactant mixture. A half-lifetime of 39 min was observed for the MLV prepared from egg-yolk phosphatidylcholine liposomes. The duration of reflectivity was prolonged drastically to a half-lifetime of 866 min by incorporating cholesterol into the MLV, although the echogenicity was decreased by such incorporation. The stabilizing effect of cholesterol for the ordinary liposomal membrane was thus ascertained in the present case of the gas-entrapping liposome. Our findings encourage the future development of improved gas-entrapping liposomes for the clinical trials of ultrasound contrast agents.

Chemical Phenomena↗

[Effect of liposome-encapsulated recombinant human superoxide dismutase (liposome-r-h-SOD) on the lung injury induced by Forssman antiserum in guinea pigs].

We investigated the effect of liposome-r-h-SOD on the lung injury induced by Forssman antiserum in guinea pigs. Intravenous injection of Forssman antiserum produced a biphasic increase in pulmonary resistance in guinea pigs. Liposome-r-h-SOD blocked this biphasic increase in a dose-dependent manner. Exudate and hemorrhage in the alveolar spaces and connective tissues were blocked by liposome-r-h-SOD. Liposome-r-h-SOD was more effective when it was injected 30 min prior to challenge than 5 min prior to challenge. On the other hand, free r-h-SOD or a mixture of free r-h-SOD and empty liposome did not block the lung injury. SOD activity in porcine endothelial cells cultured with liposome-r-h-SOD increased in a dose-dependent and time-dependent manner, while it did not increase with free r-h-SOD. Exogenous SOD was detected by immunoperoxidase staining in endothelial cells of arterioles and capillaries and in alveolar epithelial cells of the lung of guinea pigs injected with liposome-r-h-SOD. These findings suggest that superoxide radical may take part in the lung injury induced by Forssman antiserum. Liposome-r-h-SOD, which adheres to and/or is endocytosed by endothelial cells, may protect the lung from oxygen radicals.

Airway Resistance↗

Gene transfection by cationic liposomes: comparison of the transfection efficiency of liposomes prepared from various positively charged lipids.

We compared the transfection efficiency of four types of positively charged liposomes composed of (i) N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride (TMAG), dilauroylphosphatidylcholine (DLPC), and dioleoylphosphatidylethanolamine (DOPE) (1:2:2 molar ratio); (ii) 3 beta [N-(N', N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and DOPE (3:2 molar ratio); (iii) dimethyldioctadecylammonium bromide (DDAB) and DOPE (1:2.2 molar ratio); (iv) N-[1-(2,3-dioleyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTMA) and DOPE (1:1, w/w; lipofectin). Luciferase gene was used as a reporter gene. Among the cationic lipsomes used, the liposomes composed of TMAG, DOPE and DLPC showed a much higher efficiency of plasmid DNA entrapment than the other cationic liposomes tested. In the absence of serum, the cationic multilamellar vesicles (MLV) and small unilamellar vesicles (SUV) composed of TMAG, DOPE and DLPC gave highly efficient transfection. On the other hand, MLV, dehydration-rehydration vesicles (DRV), and SUV liposomes prepared with the mixtures of DC-Chol and DOPE showed similar levels of transfection efficiency. However, the cationic liposomes composed of DDAB and DOPE showed inferior efficiency, whether in the form of DRV, SUV or MLV. The transfection efficiency of lipofectin was also low. In the presence of serum, on the other hand, a considerable (about 30-50%) amount of transfection activity was still observed at 10% fetal calf serum in the cationic MLV and SUV composed of TMAG, DOPE and DLPC. Cationic MLV, composed of TMAG, DOPE and DLPC, Cationic MLV, composed of TMAG, DOPE and DLPC, can transfect plasmid DNA, not only in the adherent cell lines but also, in the suspension cell lines. These findings indicate that the transfection efficiency of cationic liposomes is affected by the lipid composition, the type of liposome, or the presence or absence of serum. They also indicate that the cationic liposomes containing TMAG, DOPE and DLPC are efficient vectors for gene transfer into cells.

Animals↗

Evidence that the effect of soya bean phosphatidylinositol-cholesterol-cyclosporin liposomes on the biosynthesis of acidic phospholipids in isolated subcellular membranes from rat liver and heart is attributable to the soya bean phosphatidylinositol-cholesterol liposomes.

This study examined the effect of adding soya bean phosphatidylinositol-cholesterol (2:1 molar ratio) liposomes and soya bean phosphatidylinositol-cholesterol (2:1 molar ratio)-cyclosporin liposomes on the biosynthesis of [3H]polyglycerophosphatides (phosphatidylglycerolphosphate, phosphatidyl-glycerol and cardiolipin) and [3H]phosphatidylinositol in mitochondria and microsomes, respectively, isolated from rat liver and heart. The results obtained with liposomes, and liposomes containing cyclosporin, established that cyclosporin did not participate in the metabolism of acidic phospholipids. In rat liver and heart mitochondria the amount of biosynthesized [3H]polyglycerophosphatides fell to one-third and a half respectively in comparison with the amounts found when liposomes were not added. The composition of [3H]polyglycerophosphatides in both mitochondria showed an increased accumulation of [3H]phosphatidylglycerolphosphate with a concomitant decrease of about 30 per cent in [3H]phosphatidylglycerol. The biosynthesis of [3H]phosphatidylinositol in both rat liver and rat heart microsomes fell to one-third of that found in the absence of liposomes. Under similar conditions the biosynthesis of [3H]cardiolipin decreased by 50 per cent in both mitochondria. The incubation of the same liposomes and liposomes containing cyclosporin with isolated rat liver mitochondria and microsomes released about 5-7 per cent of the linoleic acid. When a corresponding amount of linoleic acid was added to the incubation mixture, the biosynthesis of [3H]polyglycerophosphatides in rat liver did not change significantly, whereas in rat heart mitochondria this biosynthesis decreased by about 33 per cent. Under these conditions, the accumulation of [3H]phosphatidylglycerolphosphate and the decrease of [3H]phosphatidylglycerol was established. The biosynthesis of [3H]phosphatidylinositol in the presence of linoleic acid in rat liver and rat heart microsomes was significantly reduced. Under similar conditions the addition of stearic acid did not significantly affect the level or composition of biosynthesized [3H]polyglycerophosphatides or biosynthesized [3H]phosphatidylinositol.

Animals↗

Liposomes as cyclosporin A carriers: ESR study of cyclosporin A interaction with 1,2-dimyristoyl-sn-3-phosphatidylglycerol liposomes.

In order to study the interaction of cyclosporin A (CsA) with phosphatidylglycerol liposomes, thermally induced changes of 1,2-dimyristoyl-sn-3-phosphatidylglycerol (DMPG) liposomes and DMPG liposomes containing CsA were studied by electron spin resonance (ESR) spectroscopy using 5-, 7-, 10-, 12- or 16-nitroxide stearic acid (NO-SA) as spin probes. All liposomes were purified by Sepharose 4B column chromatography and the molar ratio of [14C]DMPG/[3H]CsA in these liposomes was found to be 31.1 +/- 0.6. ESR spectroscopy established that the gel-to-liquid crystalline phase transition of DMPG liposomes occurred sharply at 22 degrees C, shifted significantly to 26-34 degrees C in the presence of CsA, detected with 5-, 7-, 10- and 12-NO-SA probes. Furthermore, transitions at 23 degrees C and 31 degrees C were detected with 16-NO-SA probe in the same liposomes containing CsA. It was concluded that CsA interacts with both the polar head group region and the entire hydrocarbon region of DMPG and must be embedded in the hydrophobic region of liposomes.

Cyclosporine↗

Modulation of murine macrophage nitric oxide synthesis by liposomal phospholipids: correlation with liposome immune adjuvant activity.

The influence of alum and liposomal phospholipids on interferon-gamma-(IFN-gamma), IFN-gamma/N-acetylmuramyl-L-alanyl-D-isoglutamine- (MDP) or IFN-gamma/tumor necrosis factor-alpha- (IFN-gamma/TNF-alpha) induced macrophage nitric oxide (NO) synthesis has been investigated. IFN-gamma induced NO synthesis in a dose-dependent manner. TNF-alpha and MDP did not induce NO synthesis, but interacted synergistically with sub-optimal doses of IFN-gamma. Alum strongly inhibited IFN-gamma-induced NO synthesis (ID50 25 microgram/ml). Liposomes composed of dipalmitoylphosphatidylcholine (DPPC) had no effect on IFN-gamma-induced NO synthesis. IFN-gamma-induced NO synthesis was stimulated by DPPC/dimyristoylphosphatidylglycerol (DMPG) liposomes (9:1 mol ratio, ED50 45 nmol phospholipid/ml), and inhibited by DPPC/dipalmitoylphosphatidylethanolamine (DPPE) liposomes (9:1 mol ratio, ID50 > 500 nmol phospholipid/ml), and DPPC/phosphatidylserine (PS) liposomes (7:3 mol ratio, ID50 150 nmol phospholipid/ml). Alum, DPPC/PE and DPPC/PS liposomes also inhibited IFN-gamma/MDP- and IFN-gamma/TNF-alpha-induced NO synthesis. Neither alum or the liposome preparations had significant toxicity towards macrophages in vitro at concentrations that induced maximal inhibition or stimulation of IFN-gamma-induced NO synthesis. Immunization of mice with alum-adsorbed and liposome-incorporated bovine serum albumin (BSA) demonstrated that enhancement or reduction of both IgG antibody and the proportion of IgG2a/IgG2b was correlated with stimulation or inhibition of IFN-gamma-induced NO synthesis.

Adjuvants, Immunologic↗

[Liposomes as drug carrier systems. Preparation, classification and therapeutic advantages of liposomes].

Bangham et al. (1965) created first the concept of the liposome as a microparticulate lipoidal vesicle separated from its aqueous environment by one or more lipid bilayers. Later Gregoriadis and Ryman (1972) suggested to use liposomes as drug carrier systems. Nowadays liposomes are under extensive investigation for improving the delivery of therapeutic agents, enzymes, vaccines and genetic materials. Liposomes offer an excellent opportunity to selective targeting of drugs which is expected to optimize the pharmacokinetical parameters, the pharmacological effect and to reduce the toxicity of the encapsulated drugs. To understand the system it is important to know the basic properties of these lipoidal vesicles. Our aim was to focus on the lipid composition and the method of liposome preparation what determine the liposomal membrane fluidity, permeability, vesicle size, charge density, steric hindrance and stability of the liposomes as principle factors those influence the fate of liposomes, their interactions with the blood components and other tissues after systemic administration or local use.

Drug Carriers↗

Liposomal amphotericin-B in the control of experimental aspergillosis in mice: Part I--Relative therapeutic efficacy of free and liposomal amphotericin-B.

An animal model system for aspergillosis in BALB/c mice has been developed to evaluate the therapeutic efficacy of liposomal Amphotericin-B (Amp-B) and commercial Amp-B (Fungizone). Amp-B was intercalated into liposomes composed of egg phosphatidylcholine, phosphatidylethanolamine and cholesterol in a molar ratio of 6:1:3. A single dose (0.5 mg/kg body wt) of Amp-B both alone as well as in liposomal preparation was injected (i.v.) into animals infected with Aspergillus fumigatus. An increase in survival rate of animals and decrease in fungal count in lung, the most affected organ, were observed with liposomal formulation. Inclusion of Amp-B into liposomes also reduced the toxicity of the drug. Tissue distribution analysis of Amp-B by HPLC showed an increase in concentration of the drug in lung for both free and liposomal Amp-B in infected animals as compared to normal. Use of liposomal Amp-B increased the concentration of the drug in the disease affected organs such as lung, spleen. A longer persistence of the drug in the infected organs was also observed. The results suggest that inclusion of Amp-B in liposomes decreases its toxicity and improves therapeutic efficacy which at least in part could be due to more deposition and longer persistence of the drug in infected tissues.

Amphotericin B↗

Evaluation of liposome-entrapped radioactive tracers as scanning agents. Part 1: Organ distribution of liposome (99mTc-DTPA) in mice.

We describe the use of liposomes as a delivery system for radiopharmaceutical localization. Liposomes [99mTc-DTPA] were injected intravenously in mice and showed preferential uptake in the liver and spleen. There was a steady decline of activity in all organs, suggestive of destruction of liposomes with subsequent release of 99mTc-DTPA into the circulation. Alteration of uptake from liver to spleen, lung, and bone marrow was achieved by prior loading of the circulation with nonradioactive liposomes. The same effect was produced in dogs and demonstrated with scintigraphy. We also showed scintigraphically in dogs how 99mTc-DTPA, when administered entrapped in liposomes, follows the pattern of distribution of liposomes. Liposomes seem to be suitable carriers for radiopharmaceuticals. Further studies should show the possibility of directing liposomes to specific targets.

Animals↗

Effect of lipid composition on phospholipase A2-catalyzed membrane leakage in immobilized liposomes: sensitization for polychlorinated biphenyls detection with antibody affinity column tandem with fluorescent liposome column.

Phospholipase A(2) (PLA(2))-catalyzed membrane leakage can be detected by immobilized liposomes containing a self-quenching fluorescent dye, calcein, on an open column using off-line analysis with a fluorescent spectrophotometer. The calcein release was found to be affected by the pH value, incubation time, and liposome compositions. The fluorescent signal from the negatively charged liposomes hydrolyzed by PLA(2) was 5 times higher than that from neutral liposomes. We utilized this enzymatic reaction to amplify signal to detect polychlorinated biphenyls (PCBs). To achieve this goal, we conjugated an analogue of PCB, 3,4-dichloroaniline, to PLA(2). The competitive immunoreaction between the 3,4-dichloroaniline-PLA(2) conjugate and PCB samples on the anti-PCB antibody column caused the release of the bound PLA(2) conjugates in proportion to the PCB concentration. The released PLA(2) conjugates was then passed through the tandem fluorescent liposome column causing release of fluorescent dye from the liposomes. Therefore, the signal of immunocompetitive assay was amplified on the fluorescent liposome column. The tandem column system achieves a high sensitivity by detecting the PCB concentration as low as 0.5 ng/mL in less than 20 min. It has great potential in detecting other pollutants, and has been used for sensitive immunoassays.

Antibodies↗

The use of liposomal enrofloxacin for intracellular infections in Kangal dogs and visualization of phagocytosis of liposomes.

It is difficult to treat intracellular infections because of the intrinsic resistance of the microorganism to most antibiotics. Moreover, these microorganisms can survive in phagocytic cells (macrophages and neutrophils). In this study, our aims were to encapsulate an antibiotic in liposomes, which will be phagocytized as well as the microorganisms in the phagocytic cell (because liposomes were prepared using lipids which have an antigenic activity and they can be phagocytized, thus, the active substance can be transferred into the cell), and to visualise with microscopy the phagocytic activity of macrophages and neutrophils to liposomes. MLV (multilamellar vesicles) fluorescein-labeled liposomes were prepared and incubated with isolated Kangal shepherd dog macrophages and neutrophils. The phagocytosis of liposomes by monocytes was visualized step by step under the microscope. Liposomes were also observed phagocytized after incubation with neutrophils. Enrofloxacin was chosen as a model drug. Neutrophils and macrophages were isolated from Kangal shepherd dogs and infected with Staphylococcus aureus, and their phagocytic activities (PA) and microbicidal activities (MA) were determined. PA and MA values were redetermined and compared when enrofloxacin formulations were used. Liposomal enrofloxacin was found to be more effective.

Animals↗

Lyophilized liposomes as shelf items for the preparation of immunogenic liposome-peptide conjugates.

The conjugation of peptides to liposomes, while relatively simple, does represent a technical hurdle to some laboratories wishing to use such liposomes as vehicles to render peptides immunogenic. For such laboratories, having liposomes available as shelf items instead of having to prepare liposomes each time they are required may make liposomes more attractive. In this paper we report that small unilamellar liposomes bearing maleimide groups at their surface, and containing the adjuvant monophosphoryl lipid A, can be lyophilized and stored without loss of functionality or biological activity. On rehydration, peptides bearing cysteine residues are readily attached and the resulting conjugates exhibit the same immunogenicity as freshly prepared liposomes. These constructs avoid the use of protein carriers and also the use of Freund's adjuvant for raising antibodies against peptides.

Amino Acid Sequence↗

Lectin-receptor interactions in liposomes. II. Interaction of wheat germ agglutinin with phosphatidylcholine liposomes containing incorporated monosialoganglioside.

Bovine brain gangliosides incorporated into phospholipid liposomes provide receptors for wheat germ agglutinin. Purified monosialogangliosides were mixed with egg phosphatidylcholine, and unilamellar liposomes were generated. Addition of wheat germ agglutinin induced the liposomes to fuse, and gel filtration analysis revealed that the lectin was incorporated into the fused liposomes. The fusion process was studied by following the changes in the 90 degrees light scattering. Increasing the proportion of the monosialoganglioside in the liposomes was found to increase both the extent of the lectin-induced liposome fusion and the rate of the reaction; below a threshold of approx. 5 mol%, the process was extremely slow. The increase in light scattering could be prevented by the addition of the hapten inhibitor, N-acetyl-D-glucosamine (1 mM). Addition of the inhibitor, subsequent to the lectin, caused a partial decrease in light scattering due to the dissociation of unfused vesicle aggregates. Electron microscopic examination revealed that the ganglioside-containing liposomes were vesicles, 244 +/- 25 A (S.D.) in diameter. Upon addition of wheat germ agglutinin, the vesicles appeared to fuse to form larger vesicles, corresponding to dimers and trimers of the initial vesicles. Inhibition studies with a variety of monosaccharides indicated that the sialic acid moieties present in the ganglioside acted as the lectin-receptor sites. This was confirmed by the observation that wheat germ agglutinin did not interact with phosphatidylcholine vesicles containing desialyated ganglioside.

Binding Sites↗

Antibody-dependent phagocytosis of haptenated liposomes by human neutrophils is dependent on the physical state of the liposomal membrane.

In the present study we have examined the response of human neutrophils to specific antibody-dependent stimulation by spin-label haptenated fluid phase and solid phase liposomes. Both fluid and solid liposomal antigens are shown to stimulate the neutrophil respiratory burst to approximately equivalent degrees as assessed by measurement of oxygen consumption or oxidation of [1-14C]glucose to 14CO2. In contrast, release of superoxide and hydrogen peroxide from the neutrophils is stimulated to a significantly greater degree by fluid-phase liposomes than by the equivalent solid-phase liposomes. This apparent discrepancy is shown to be due to an inability of the neutrophils to phagocytose fluid-phase liposomes under conditions in which solid-phase liposomes are readily phagocytosed. A fluorescence assay, which does not depend upon binding measurements, has been developed in order to quantitate liposomal phagocytosis.

Antibodies↗