Biomedical subjects

R Löfgren

Publications and source records attributed to R Löfgren.

5 recordsLinked to original sources

PubMed2001

Tumour necrosis factor-alpha potentiates CR3-induced respiratory burst by activating p38 MAP kinase in human neutrophils.

CR3 and Fc gamma Rs are the main receptors involved in the phagocytic process leading to engulfment and killing of microbes by production of reactive oxygen intermediates (ROI) and degranulation. Various inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS), are known to prime neutrophils leading to increased bactericidal responses, but the underlying mechanism of priming has only been partially elucidated. The purpose of this study was to investigate how TNF-alpha primes neutrophils for subsequent stimuli via either CR3 or Fc gamma R. The receptors were specifically activated with pansorbins (protein-A-positive Staphylococcus aureus) coated with anti-CR3, anti-Fc gamma RIIa, or anti-Fc gamma RIIIb monoclonal antibody. Activation of neutrophils with these particles resulted in ROI production as measured by chemiluminescence. Anti-CR3 pansorbins induced the most prominent ROI production in neutrophils. TNF-alpha potentiated the CR3-mediated respiratory burst but had little effect on that mediated by Fc gamma Rs. The priming effect of TNF-alpha on CR3-mediated ROI production is associated with an increased activation of p38 MAPK as well as tyrosine phosphorylation of p72(syk). Pretreatment of neutrophils with the inhibitors for p38 MAPK and p72(syk) markedly suppressed the respiratory burst induced by CR3. Furthermore, TNF-alpha induced about a three-fold increase in the expression of CR3 in neutrophils, an effect which is blocked by the p38 MAPK inhibitor. Taken together, these results showed that TNF-alpha potentiates the CR3-mediated respiratory burst in neutrophils not only by triggering a p38 MAPK-dependent up-regulation of CD11b/CD18 but also by modulating the signalling pathways.

CD18 Antigens↗

PubMed1999

CR3, FcgammaRIIA and FcgammaRIIIB induce activation of the respiratory burst in human neutrophils: the role of intracellular Ca(2+), phospholipase D and tyrosine phosphorylation.

Human neutrophils express two different types of phagocytic receptors, complement receptors (CR) and Fc receptors. In order to characterize the different signaling properties of each receptor we have used non-adherent human neutrophils and investigated CR3, FcgammaRIIA and FcgammaRIIIB for their signaling capacity. Selective activation of each receptor was achieved by coupling specific antibodies to heat-killed Staphylococcus aureus particles, Pansorbins, through their Fc moiety. Despite the fact that these particles are not phagocytosed, we show that addition of Pansorbins with anti-CD18 antibodies recognizing CR3 induced prominent signals leading to a respiratory burst. Stimulation with anti-FcgammaRIIIB Pansorbins induced about half of the response induced by anti-CR3 Pansorbins, whereas anti-FcgammaRIIA Pansorbins induced an even weaker signal. However, FcgammaRIIA induced strong phosphorylation of p72(syk) whereas FcgammaRIIIB induced only a very weak p72(syk) phosphorylation. During CR3 stimulation no tyrosine phosphorylation of p72(syk) was seen. Both phospholipase D and NADPH oxidase activities were dependent on intracellular calcium. This is in contrast to tyrosine phosphorylation of p72(syk) that occurred even in calcium-depleted cells, indicating that oxygen metabolism does not affect p72(syk) phosphorylation. Inhibitors of tyrosine phosphorylation blocked the respiratory burst induced by both FcgammaRIIA and FcgammaRIIIB as well as CR3. This shows that tyrosine phosphorylation of p72(syk) is an early signal in the cascade induced by FcgammaRIIA but not by CR3.

Antibodies, Monoclonal↗

PubMed1996

Chamber for indirect calorimetry with improved transient response.

A chamber for indirect calorimetry has been constructed that utilises previously published general equations for the calculation of respiration. Owing to the large size of the chamber, the changes in gas concentration caused by a subject are very small. Therefore, algorithms are developed for noise suppression and trend identification. Using the exact solution of the equations for steady state, each gas concentration is fitted by a least square method to two connected exponential segments, of variable length, for the preceding 30 min period. Independently of the location of the join between the two segments, the gas concentration and its time derivative are evaluated at -15 min. This process is repeated, and its results are presented once every minute. As proven by gas injection tests, this procedure gives an instantaneous response to a single change in respiration, a correct averaging of repeated changes in respiration with periods of less than 15 min and noise suppression. It is concluded that this chamber is useful not only for traditional 24 h energy expenditure measurements, but also for experiments requiring rapid responses.

Algorithms↗

PubMed1994

A multicompartment body composition technique based on computerized tomography.

The objective of this study was to develop a body composition method based on computerized tomography (CT) which would make it possible to divide the body into multiple compartments at the tissue and organ level. Eight healthy males (21-42 years old) with BMIs ranging from 18.6 to 25.3 kg/m2 were used for the methodological development. Areas of tissues, organs and air/gas were measured in 28 cross-sectional scans having defined and identical positions in all examined subjects. The area determinations were performed with the following attenuation intervals (given in Hounsfield units, HU): air, gas and lungs: -1001 to -191 HU; adipose tissue (AT): -190 to -30 HU; all other soft tissues and organs: -29 to +151 HU; skeleton: 152 to 2500 HU. Various tissue and organ areas in the -29 to +151 HU interval were obtained by means of cursor circumscriptions, while area determinations in other intervals were based on the number of pixels fulfilling given attenuation criteria. Volumes of tissues, organs and gas were obtained from corresponding areas and the distances between the scans. The body was divided into 12 main volumes of tissues, organs and gas that could be further subdivided by region. The main volumes observed (in litres; mean +/- s.d.) were: skeleton (subdivisible into dense skeleton, red and yellow bone marrow): 8.7 +/- 0.9; skeletal muscle: 31.9 +/- 5.1; visceral AT (subdivisible into intra- and retroperitoneal, cardiac, other thoracic AT): 3.0 +/- 1.7; intra- and retroperitoneal organs other than AT: 4.6 +/- 0.8; gastrointestinal gas: 0.25 +/- 0.09; heart: 0.61 +/- 0.12; lungs and bronchial air: 5.1 +/- 1.1; other thoracic organs: 0.32 +/- 0.08; mammary glands: 0.001 +/- 0.004; CNS (subdivisible into brain and contents of spinal channel): 1.6 +/- 0.15; air in sinuses and trachea: 0.19 +/- 0.05; subcutaneous AT: 11.6 +/- 2.8; skin: 2.4 +/- 0.39. Precision errors as determined from double analyses of different tissue volumes ranged from 0.01 to 0.3 litres. For validation purposes, CT-estimated organ weights were obtained by multiplying organ volumes by their assumed densities. The sums of all organ weights were then compared with the measured body weights. The error calculated from the individual differences between these weights was 0.6 kg (0.85%). The multicompartmentation technique described has a high validity and reproducibility and is applicable over a wide range of medical fields which require body composition measurements at the tissue and organ level.

Abdomen↗

PubMed1993

Beta 2 integrin engagement triggers actin polymerization and phosphatidylinositol trisphosphate formation in non-adherent human neutrophils.

Beta 2 integrins are involved in the adhesion of leukocytes to other cells and surfaces. Although adhesion is required for cell locomotion, little is known regarding the way beta 2 integrin-receptors affect the actin network in leukocytes. In the present study filamentous actin (F-actin) levels in non-adherent human neutrophils have been measured by phalloidin staining after antibody cross-linking of beta 2 integrins. Antibody engagement of beta 2 integrins resulted in a rapid and sustained (146 and 131% after 30 and 300 s, respectively) increase in the neutrophil F-actin content. This is in contrast to stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), which causes a prompt and pronounced but rapidly declining rise in F-actin (214 and 127% after 15 and 300 s, respectively). Priming neutrophils with 1 nM PMA, a low concentration that did not influence the F-actin content per se, increased the magnitude of the beta 2 integrin-induced response but had no effect on the kinetics (199% after 30 s and 169% after 300 s). Removal of extracellular Ca2+ only marginally affected the beta 2 integrin-induced F-actin response for cells that were pretreated with PMA whereas the response for nonprimed cells was reduced by half. This suggests that even though extracellular Ca2+ has a modulatory effect it is not an absolute requirement for beta 2 integrin-induced actin polymerization. beta 2 integrin engagement did not affect the resting cellular level of cAMP arguing against a role of cAMP in beta 2 integrin-induced actin assembly.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗