PubMed Health⌕ Search

Biomedical subjects

Martinus Løvik

Publications and source records attributed to Martinus Løvik.

At least 19 recordsLinked to original sources
PubMed2007

Popliteal lymph node (PLN) assay to study adjuvant effects on respiratory allergy.

Different variants of the popliteal lymph node (PLN) assay have been published. Here we describe the adjuvant popliteal lymph node assay, an immune response assay to study the adjuvant activity of soluble substances as well as particulate matter. The substance to be studied for adjuvant activity is injected into the hind footpad of mice or rats together with an antigen. Adjuvant activity is determined as the increase in PLN weight and cell numbers in animals receiving antigen together with the substance under study, compared with PLN weight and cell numbers in animals given the antigen without the substance in question, and animals given the putative adjuvant alone. Because lymph node weight and cell numbers are immunologically non-specific parameters, specific immune response assays like serum antibody responses or antibody-forming cell numbers should additionally be performed. Different antigens and immune response assays may be used, depending on the research question asked. In relation to respiratory (or food) allergy, the assays should as a minimum include determination of specific IgE in serum, and preferably also IgG1 (mouse). Serum specific IgG2a antibody determination may be added to get an indication of the Th1-Th2-balance of the response. The adjuvant PLN assay, with cellular response assays performed in the draining popliteal lymph node and antibody determinations in serum, requires small amounts of test material. The assay offers a practical, sensitive and reproducible method to determine the adjuvant activity of soluble substances as well as particulate material, with the possibility to also perform mechanistic studies.

Adjuvants, Immunologic↗
PubMed2006

Detection of allergens adsorbed to ambient air particles collected in four European cities.

Air pollution has been implicated as one of the factors responsible for the increased incidence of allergic diseases observed in recent years. High concentrations of air pollutants may promote airway sensitization by acting as adjuvants. Ambient particles as carriers of adsorbed allergens are, therefore, of special interest since they may act as mediators of inflammatory as well as allergic responses. Ambient air particles from four cities in Europe were collected, in three different seasons, to examine the variation of allergens and their possible binding to the pollution particles. The particle fraction, PM10, was collected on polycarbonate filters using a low-volume sampling regime. The presence of pollen allergens, latex and beta-glucans was investigated using an immunogold labelling method directly on the collection filters. Scanning electron microscopy revealed mainly the classical carbon particles and aggregates determined to originate from vehicle exhaust. The immunogold labelling visualised in the backscatter electron imaging mode, showed that allergens from pollens, latex and also beta-glucans were bound to and, hence, transported by the combustion particles in ambient air. Thus, combustion particles in ambient air are carriers of allergens and act as depots of allergens inhaled into the airways.

Air↗
PubMed2005

IgE-mediated sensitisation, rhinitis and asthma from occupational exposures. Smoking as a model for airborne adjuvants?

OBJECTIVE: Airborne pollutants with adjuvant effect, called airborne adjuvants, may promote IgE-sensitisation and development of allergic airway diseases. Smoking and occupational allergen exposures were reviewed to establish a general and verified framework for hazard identification and risk assessment of adjuvant effects of airborne pollutions. METHODS: The relative risks and the attributable risks of adjuvant effect of smoking were determined for co-exposures with green coffee and castor beans, ispaghula, senna, psyllium, flour and grain dust, latex, laboratory animals, seafood, enzymes, platinum salts, organic anhydrides, or reactive dyes. RESULTS: Adjuvant effects of smoking depended on the types of allergen, but not on whether sensitisation or allergy was promoted by atopy-the hereditarily increased ability to increase IgE formation. CONCLUSION: Promotion of IgE sensitisation in humans and in animals may serve for hazard identification of adjuvant effects. Risk assessment has been based mainly on epidemiological studies, which are sensitive to confounding factors. This highlights the need to develop appropriate animal models for risk assessment.

Adjuvants, Immunologic↗
PubMed2005

The allergy adjuvant effect of particles - genetic factors influence antibody and cytokine responses.

BACKGROUND: There is increasing epidemiological and experimental evidence for an aggravating effect of particulate air pollution on asthma and allergic symptoms and, to a lesser extent, on allergic sensitization. Genetic factors appear to influence not only the magnitude, but also the quality of the adjuvant effect of particles with respect to allergen-specific IgE (Th2-associated) and IgG2a (Th1-associated) responses. In the present study, we aimed to investigate how the genetic background influences the responses to the allergen and particles alone and in combination. We examined how polystyrene particles (PSP) affected the IgE and IgG2a responses against the model allergen ovalbumin (OVA), after subcutaneous injection into the footpad of BALB/cA, BALB/cJ, NIH and C3H/HeN mice, Further, ex vivo IL-4, IFN-gamma and IL-10 cytokine secretion by Con A-stimulated cells from the draining popliteal lymph node (PLN) five days after injection of OVA and PSP separately or in combination was determined. RESULTS: PSP injected with OVA increased the levels of OVA-specific IgE antibodies in all strains examined. In contrast, the IgG2a levels were significantly increased only in NIH and C3H/HeN mice. PSP in the presence of OVA increased cell numbers and IL-4, IL-10 and IFN-gamma levels in BALB/cA, NIH and C3H/HeN mice, with the exception of IFN-gamma in NIH mice. However, each mouse strain had their unique pattern of response to OVA+PSP, OVA and PSP, and also their unique background cytokine response (i.e. the cytokine response in cells from mice injected with buffer only). CONCLUSION: Genetic factors (i.e. the strain of mice) influenced the susceptibility to the adjuvant effect of PSP on both secondary antibody responses and primary cellular responses in the lymph node, as well as the cellular responses to both OVA and PSP given separately. Interestingly, PSP alone induced cytokine responses in the lymph node in some of the mouse strains. Furthermore, we found that the ex vivo cytokine patterns did not predict the in vivo Th2- and Th1-associated antibody response patterns in the different mouse strains. The results indicate that insoluble particles act by increasing the inherent response to the allergen, and that the genetic background may determine whether an additional Th1-associated component is added to the response.

Adjuvants, Immunologic↗
PubMed2005

[Mustard--an important food allergen?].

BACKGROUND: The European Parliament and the Council of the European Union have issued a new directive on information on the label about the ingredients present in foodstuffs. Twelve foods causing hypersensitivity are now subject to particularly strict labelling rules. Among these foods is mustard, which until now has been little recognised as a food allergen in Norway. MATERIALS AND METHODS: Literature searches in Medline were performed and supplemented by manual searches of reference lists. RESULTS: Since the first published case of mustard allergy in 1980, a number of case reports and patient series have been published. Most reports come from certain regions of France, and a majority of the studies have been performed by a limited number of investigators. Symptoms triggered by mustard cover the whole range from full-blown systemic anaphylactic reactions to pollen-food allergy syndrome-like local reactions. Frequently, reactions appear to be serious. Mustard allergy has on many instances been found in small children. Cross-reactivity apart from that among different types of mustard does not appear to be a clinical problem. Mustard allergens are resistant to heat and food processing. INTERPRETATION: With more attention being given to mustard as a food allergen because of the new labelling rules, it will most likely soon become apparent whether mustard is a food allergen of importance in Norway. The Norwegian national reporting system and register of severe allergic reactions to food will be an important tool in this context.

Cross Reactions↗
PubMed2005

Ambient air particles from four European cities increase the primary cellular response to allergen in the draining lymph node.

In the RAIAP (respiratory allergy and inflammation due to ambient particles) project, qualitative properties of ambient air particles from Amsterdam, Oslo, Lodz and Rome were investigated in relation to inflammation and allergy. Most collected particle fractions were found to increase the allergen-specific IgE and IgG2a responses after subcutaneous injection of particles with allergen in mice. However, some fractions appeared to skew the antibody response towards more Th1- or Th2-associated antibody isotypes, and the fine fractions were found to be more potent than the coarse fractions with regard to IgE adjuvant activity. In the present study we investigated the cellular response in the draining lymph node 5 days after a subcutaneous injection of selected RAIAP particle fractions. The particles (100 microg) were injected into both hind footpads of BALB/cA mice, in the presence or absence of the allergen ovalbumin (OVA, 50 microg). We also studied if the coarse and fine RAIAP particle fractions affected the cellular responses to OVA differently. The number of lymph node cells, as well as the relative number of B and T lymphocytes and T helper cells were determined. Expression of cell surface molecules (MHC class II, CD86 and CD23) and ex vivo cytokine production (IL-4, IL-10 and IFN-gamma) by the lymph node cells were measured. Overall, particles in the presence of allergen enhanced the levels of the various cellular parameters compared to allergen alone or particles alone. In the absence of allergen, ambient air particles, in contrast to diesel exhaust particles, marginally affected some cellular parameters. By histological examination of the lymph node, the particles appeared to be scattered between the lymphocytes, often localised within macrophage-like (acid phosphatase positive) cells. The cell parameters measured could, for the individual sample, neither predict the degree of a Th2- or Th1-skewed antibody response, nor the stronger antibody adjuvant capacity of the fine than the coarse particle fractions. In conclusion, we have shown that coarse and fine ambient air particles from different European cities enhance the cellular response in the draining lymph node after injection with an allergen. In the absence of allergen, ambient particles only marginally affected the cellular parameters.

Air Pollutants↗
PubMed2005

The IgE adjuvant effect of particles: characterisation of the primary cellular response in the draining lymph node.

Diesel exhaust particles, and polystyrene particles (PSP) as a model for the insoluble particle core, have an adjuvant effect on allergen-specific IgE production in mice. We therefore examined the primary immune response in the draining popliteal lymph node (PLN) to the allergen ovalbumin (OVA) injected together with polystyrene particles into the footpad of BALB/cA mice. Similar numbers of particle-containing cells were observed in the draining lymph node on day 1 after injection of PSP alone or OVA + PSP, the numbers increasing continuously until day 21. The total lymph node cell numbers increased three to four times in the OVA + PSP group compared to both OVA and PSP groups, peaking on day 5. The increase in B cell numbers was twice the increase in T cell numbers. On day 5, OVA + PSP increased the expression of most surface markers measured (MHC class II, CD86, CD23, CD69) compared to OVA and PSP. Further, the ex vivo production of IL-4 and IL-10 by PLN cells from OVA + PSP-injected animals was increased. In conclusion, whereas PSP alone did not influence any of the immunologic markers studied, the adjuvant effect of PSP on the IgE antibody response to OVA was associated with an early increased primary cellular response in the draining lymph node.

Adjuvants, Immunologic↗
PubMed2005

Development of the "Cell Chip": a new in vitro alternative technique for immunotoxicity testing.

Predictive testing of immunotoxicity associated with chemical compounds is complicated and cannot be accomplished with a single test. As most of the existing tests for immunotoxicity employ experimental animals, there is an increasing need for alternative tests in vitro. We have developed a new system for in vitro immunotoxicity testing, which employs changes in cytokine expression observed in vitro as an endpoint indicating potential for perturbation of the immune system in vivo. This system named "fluorescent cell chip" (FCC) is based on a number of genetically modified cell lines that regulate the expression of a transgene coding for fluorescent protein enhanced green fluorescent protein (EGFP) in a similar way as they regulate expression of IL-1beta, IL-2, IL-4, IFN-gamma, IL-10, TNF-alpha, and beta-actin. Morphological and functional features of selected cell lines expressing EGFP under the control of cytokine promotors were compared with maternal cell lines and this comparison showed that critical functional features of the maternal cell lines were preserved in EGFP expressing cells. Two chemicals with known immunotoxic activities, cyclosporine A and potassium tetrachloro-platinate(II), mediated compound-specific pattern of inhibition and activation of reporter gene expression. Thus, the "fluorescent cell chip" has demonstrated potential for application as a predictive screening test for immunomodulatory activities of chemicals. The major advantage of this approach is the possibility to apply this test in high throughput screening of high number of compounds for their well defined biological activity.

Animals↗
PubMed2004

The capacity of particles to increase allergic sensitization is predicted by particle number and surface area, not by particle mass.

Particle exposure has traditionally been monitored as mass concentration of PM10 (particles with an aerodynamic diameter less than 10 microm), more recently also as PM2.5. The mass concentration is strongly influenced by the large particles. Therefore, particle mass is a poor measure for characterizing the amount of the small, possibly more biologically potent particles. We used polystyrene particles (PSP) ranging in diameter from 0.0588 to 11.14 microm, carbon black (CB), and diesel exhaust particles (DEP), to study the adjuvant effect of particles on the immune response to the allergen ovalbumin (OVA) after sc injection into the footpad of BALB/cA mice. At a given mass dose, the small particles (0.0588 and 0.202 microm PSP, CB, and DEP) increased the allergen-specific IgE serum levels to a substantially higher degree than the larger particles (1.053, 4.64, and 11.14 microm PSP). Further, in the draining lymph node during the primary response, the fine particles (0.202 microm) with OVA increased cell numbers, expression of surface markers (CD19, MHC class II, CD86, and CD23) and ex vivo production of IL-4 and IL-10, whereas the largest (11.14 microm) particles did not. Linear regression analyses indicated that the IgE response was not predicted by particle mass (R2 = 0.06), but was predicted by the total particle surface area (R2 = 0.64), number of particles (R2 = 0.62), and particle diameter (R2 = 0.58). In conclusion, we found that fine particles exerted stronger adjuvant effects on allergic responses than larger particles at equal mass doses. Consequently, the dose described as total particle surface area or particle number predicts the adjuvant effect of particles better than the currently used particle mass.

Adjuvants, Immunologic↗
PubMed2004

A case of peanut cross-allergy to lupine flour in a hot dog bread.

BACKGROUND: In a case monitored by the Norwegian National Register for Severe Allergic Reactions to Food, a patient with peanut allergy experienced an allergic reaction after eating a particular brand of hot dog bread. The aim of this study was to identify the eliciting allergen. METHODS: Extracts from the hot dog bread and reference material from peanut, lupine and lupine-fortified food products were analysed by immunochemical methods with patient serum and a new polyclonal anti-lupine antibody. RESULTS: Evidence could be provided that the hot dog bread contained proteins from lupine but not from peanut. CONCLUSION: Crossed peanut-lupine allergy can have clinical significance. A peanut-allergic patient reacted against hidden lupine protein in a hot dog bread. Presented with our results, the producer confirmed the use of lupine flour and changed the ingredient list.

Adult↗
PubMed2004

Respiratory allergy adjuvant and inflammatory effects of urban ambient particles.

PM(10) and PM(2.5) fractions were collected by high-volume cascade impactors during 4-week periods in spring, summer and winter seasons in Amsterdam, Lodz, Oslo and Rome and at a Dutch seaside site. The samples were screened for respiratory allergy potential with the mouse popliteal lymph node (PLN) and the ELISA-based IgE antibody assays. For inflammatory screening, release of the cytokine macrophage inflammatory protein-2 (MIP-2) from primary rat type 2 cells was determined. Most fractions gave an increase in the lymph node response with the model allergen ovalbumin indicating adjuvant activity. Some of the coarse fractions gave a lymph node response even in the absence of ovalbumin, caused probably by non-specific inflammation. With the exception of a few of the coarse fractions, all ambient fractions increased the production of specific IgE. Fine particles had stronger adjuvant effect than coarse particles. A significant increase in the allergen specific IgG2a response was observed for the fine and some of the coarse fractions, indicating a non-allergic Th1 response. No consistent differences in adjuvant effects between the locations were observed. Particle samples collected in the different European cities differed in their potency to induce MIP-2 in type 2 cells. Coarse fractions of the urban particles samples, as well as the coarse fraction collected at the seaside, were more potent than the fine fractions to induce MIP-2. With respect to seasonal variations, the coarse fractions collected in summer seemed to be the most potent.

Air Pollutants↗
PubMed2003

The effect of endotoxin on the production of IgE, IgG1 and IgG2a antibodies against the cat allergen Fel d 1 in mice.

BACKGROUND: Endotoxin/LPS is ubiquitous in our environment. The question whether lipopolysaccharide (LPS) is beneficial or disease-promoting in relation to asthma and allergy has been raised in several recent studies. Some have reported a positive correlation between the level of LPS in house dust and the symptoms of asthmatic children. Others have found that exposure to LPS appears to protect against the development of atopic disease in children. OBJECTIVES: We performed a study in mice to examine the antibody response after subcutaneous immunization with LPS and the cat allergen Fel d 1. We asked whether LPS would increase the response and direct the antibody production towards an allergic (IgE), or non-allergic (IgG2a) antibody profile. In rodents both IgE and IgG1 are antibodies produced under Th2-dependence and IgG2a antibodies under Th1-dependence. Also, when LPS and Fel d 1 are introduced to the immune system, we asked whether the timing of the two agents relative to each other is crucial. METHODS: The mice were injected subcutaneously with LPS and/or Fel d 1 four times in various orders. IgE, IgG1 and IgG2a antibodies specific to Fel d 1 were measured in serum using ELISA. RESULTS: A strong antibody response, both for IgE, IgG1 and IgG2a, was observed only when Fel d 1 and LPS were injected simultaneously, and in particular after repeated injections. CONCLUSION: A strong specific antibody response was observed, both for IgE, IgG1 and IgG2a, only when LPS was introduced to the immune system together with the cat allergen Fel d 1. No such adjuvant effect was observed when LPS was introduced alone prior to or subsequent to the allergen. The resulting antibody response was not polarized in terms of Th1- or Th2-dependence.

Animals↗
PubMed2002

[Air pollution, asthma and allergy--the importance of different types of particles].

BACKGROUND: Particulate air pollution has been much discussed in Norway during the last few years. Coarse particles from asphalt are likely to have quite different properties than the far smaller particles from diesel exhaust. MATERIALS AND METHODS: On the basis of data from the literature and our own research, we discuss the health problem of different types of particles with a focus on allergy and respiratory symptoms. RESULTS: Diesel exhaust particles have well-documented adverse effects in relation to allergic airway disease. They increase symptoms load in already allergic individuals and also seem to contribute to the increased prevalence of allergy. PM10 is today measured on the basis of weight, not on number. Diesel exhaust particles are much smaller than road surface particles; hence PM10 measurements reflect road surface dust pollution more than exhaust particles. INTERPRETATION: Focus should now be given to diesel exhaust particles in order to reduce the adverse health effects of particulate air pollution in Norwegian cities.

Air Pollutants↗
PubMed2002

Blood and spleen lymphocytes as targets for immunotoxic effects in the rat--a comparison.

Traditionally, immunotoxicological studies in the rat have been performed by measuring the effect of chemical substances on spleen lymphocytes in vivo and in vitro. However, rat blood lymphocytes may be more relevant than spleen cells for comparison with human blood lymphocytes. Further, lymphocytes in blood may be a more sensitive indicator of immunotoxic effects than spleen lymphocytes. Finally, in longitudinal studies peripheral blood specimens can be collected repeatedly from the same animals, thereby reducing the number of animals sacrificed and, possibly, experimental variation. We compared blood and spleen lymphocyte parameters in rats treated with a single dose of the immunosuppressant cyclophosphamide (CY), monitoring effects on blood and spleen lymphocytes by immunophenotyping. We also performed repeated bleedings to demonstrate the feasibility of following the time course of induced changes in the same animals. Immunophenotyping as well as total mononuclear cell counts consistently showed as large or lager effects of CY in blood lymphocytes than in spleen cells. Further, the measured effects in blood lymphocytes became statistically significant at an earlier time point, compared to spleen cells. Repeated bleedings of the same animals illustrated that blood specimens drawn from a peripheral vein give sufficient numbers of cells to perform immunotoxicological tests.

Animals↗