Schistosoma mansoni: further studies of the interaction between schistosomula and granulocyte-derived cationic proteinsin vitro

Parasitology ◽  
1984 ◽  
Vol 88 (3) ◽  
pp. 491-503 ◽  
Author(s):  
Diane J. McLaren ◽  
C. G. B. Peterson ◽  
Per Venge

SUMMARYPurified eosinophil and neutrophil cationic proteins isolated from the lysosomal secretion granules of human leucocytes have been tested for cytotoxic capacity against lung-stage schistosomula ofSchistosoma mansoni in vitro. Eosinophil cationic protein (ECP) caused paralysis but not death at high concentration; this effect was reversible and involved no gross pathological manifestations. Eosinophil protein X (EPX) and neutrophil cationic protein (NCP) were highly toxic at concentrations of 10−5mol/1, and induced paralysis at sublethal concentrations. These two proteins exerted their cidal effect principally against the subtegumental musculature and internal tissues of the parasite rather than against the surface syncytium and tegumental outer membrane. ECP and NCP were shown to bind to lung worms at paralysing concentrations, but this binding occurred independently of the charge of the parasite surface. Of several control proteins tested, only protamine was capable of destroying lung-stage parasites; the manifestations of damage were different, however, from those induced by the granulocyte-derived proteins. Parallel assays demonstrated that EPX also possessed cytotoxic capacity against newly transformed schistosomula, but it was less efficient than ECP in this respect. The data are discussed in relation to potential post-skin mechanisms of challenge attrition in the immunized host.

2006 ◽  
Vol 13 (5) ◽  
pp. 584-593 ◽  
Author(s):  
Claus M. Reimert ◽  
Colin M. Fitzsimmons ◽  
Sarah Joseph ◽  
Joseph K. Mwatha ◽  
Frances M. Jones ◽  
...  

ABSTRACT Eosinophil activity in vivo and in vitro was studied in relation to infection intensities and plasma cytokine profiles of 51 Schistosoma mansoni-infected Ugandan fishermen before treatment and 24 h and 3 weeks posttreatment. Blood eosinophil numbers significantly declined 24 h posttreatment, but significant eosinophilia had developed by 3 weeks posttreatment. Cellular eosinophil cationic protein (ECP) content increased significantly during the transient eosinopenia but was significantly reduced 3 weeks later. No similar reduction in cellular eosinophil protein X (EPX) content was seen. Before treatment, S. mansoni infection intensity was positively correlated with 24-h boosts in plasma interleukin-5 (IL-5) and IL-6 levels, which were in turn negatively correlated with the posttreatment fall in eosinophil numbers. Significant correlations were observed between pretreatment infection intensities and plasma IL-10 and eotaxin levels. Treatment induced significant fluctuations in plasma IL-5, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), and eotaxin levels. Optimal relative release of ECP and EPX in vitro was detected in S. mansoni soluble egg antigen-stimulated cultures during transient eosinopenia. Our data suggest that blood eosinophils are activated during S. mansoni infection and that treatment induces a burst in released antigens, causing increased production of IL-5, IL-6, IL-10, and eotaxin; a drop in TNF-α levels; and a transient sequestration of eosinophils, which leaves fewer degranulated eosinophils in the circulation 24 h posttreatment, followed by the development of eosinophilia 3 weeks later. During these events, it appears that preferential release of ECP occurs in vivo. Moreover, it is possible that infection intensity-dependent levels of plasma IL-10 may be involved in the prevention of treatment-induced anaphylactic reactions.


CHEST Journal ◽  
1993 ◽  
Vol 103 (2) ◽  
pp. 475-478 ◽  
Author(s):  
Tom Pettersson ◽  
Henrik Riska ◽  
Seppo Sutinen ◽  
Matti Klockars ◽  
Christer Peterson

1993 ◽  
Vol 84 (4) ◽  
pp. 391-399 ◽  
Author(s):  
Claus Kroegel ◽  
Ann Dewar ◽  
Tatsuo Yukawa ◽  
Per Venge ◽  
Peter J. Barnes ◽  
...  

1. Purified human eosinophils from asthmatic patients were stimulated with platelet-activating factor in vitro and examined for morphological changes by transmission electron and light microscopy. Changes were also evaluated by morphometric analysis and were related to the platelet-activating factor-stimulated release of granular eosinophil cationic protein. 2. Stimulation of eosinophils with platelet-activating factor induced a dose-dependent shape change, including the elongation of cells, loss of microvilli and the formation of lamellipodia. This effect was maximal at 25 min and was reversible. 3. Stimulation with platelet-activating factor also induced granule movement to the cell periphery and fusion of adjacent granules. Granules became swollen and vesiculated, whereas both the matrix and core showed evidence of solubilization. 4. There was a time-dependent secretion of eosinophilic cationic protein from human eosinophils upon stimulation with platelet-activating factor which occurred without significant lactate dehydrogenase release. 5. Morphometric analysis of the transmission electron micrographs indicated a significant reduction in cytoplasmic area after 10 min of incubation with platelet-activating factor from 39.0 ± 1.7 μm2 for untreated eosinophils to 33.2 ± 2.3 μm2 (P < 0.02) for platelet-activating factor-treated cells, underscoring the observation that the cells change from spherical to ellipsoidal. No significant increase in the perimeter of the cells was found. 6. The number of granule-profiles in platelet-activating factor-stimulated eosinophils was slightly reduced when compared with control, and an increase in granule area was observed 10 min after platelet-activating factor challenge (0.215 ± 0.011 μm2 versus 0.246 ± 0.016 μm2). 7. Human eosinophils from patients with asthma stimulated with platelet-activating factor undergo both cellular and granular alterations and reorganization which parallel the release of granular eosinophil basic protein.


1994 ◽  
Vol 3 (3) ◽  
pp. 223-227 ◽  
Author(s):  
L. K. Poulsen ◽  
C. M. Reimert ◽  
C. Bindslev-Jensen

To investigate whether eosinophils are stimulatedin vivoor have acquired an increased susceptibility to stimuli from the coagulation cascade, the release of eosinophil proteins was compared for three groups of donors with different levels of serum IgE. (1) with atopic dermatitis (s-IgE > 5000 IU/ml,n= 11); (2) with inhalant allergy (200 < s-IgE < 2 000 IU/ml,n= 10); and (3) non-allergic (s- IgE < 100 IU/ml,n= 10). The levels of eosinophil cationic protein and eosinophil protein X (ECP, EPX) were determined in serum (clotting time = 2.0 h) and plasma. Serum and plasma ECP in normal donors demonstrated large intra-personal variations (C.V. 50–80%), but serum-ECP (mean 8.1 ng/ml) was clearly distinguishable from plasma ECP (mean 1.0 ng/ml) by a factor of 8 (range: 5.6–11.6). The ECP released during clotting was markedly increased in the atopic dermatitis group (serum:plasma ratio 13.5,p<0.003) compared with the other groups (6.7 and 5.6). EPX, having a higher plasma level, demonstrated a less pronounced release (serum: plasma ratios 2.0, 1.7 and 1.4), with no statistical difference between donor groups. Considering all donors together the levels of ECP and EPX in plasma and in serum were correlated to the number of eosinophils (coefficients of correlation 0.54-0.58,p<0.002).


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