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  • 1
    Electronic Resource
    Electronic Resource
    THERAPEUTIC RAMIFICATIONS OF THE INTERACTION OF COMPLEMENT, GRANULOCYTES, AND PLATELETS IN THE PRODUCTION OF ACUTE LUNG INJURY (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 384 (1982), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1982.tb21395.x
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  • 2
    Electronic Resource
    Electronic Resource
    Synergy among agents inhibiting granulocyte aggregation (1982)
    Springer
    Inflammation 6 (1982), S. 169-176 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent evidence suggests complement (C) -stimulated granulocytes (PMNs) are important in a variety of diseases, including shock and myocardial infarction (MI). Corticosteroids inhibit PMN response to C and show promise in some studies of shock and MI, but their use has not become routine for several reasons. Synergy was sought among agents inhibiting PMN aggregation in vitro in response to activated C: methylprednisolone (MP), with a 50% inhibitory dose (AD50) of 0.6 mg/ml; ibuprofen (IBU), with AD50 of 1.0 mg/ml, and betahistine (BH), with AD50 of 1.6 mg/ml. Simultaneous use of all three agents produced 3.4-fold synergy; 3-fold synergy obtained between IBU + MP and IBU + BH, while 1.5-fold synergy was noted between MP + BH. Further, MP and IBU were at least additive in inhibiting · O 2 − a generation by FMLP-stimulated PMNs and in blocking directed migration. In a preliminary in vivo test of this finding, cats were given MP and IBU—in known individually ineffective doses—immediately prior to coronary artery ligation. Neither MP nor the low dose of IBU chosen limited the size of the resultant MI, while both agents together reduced MI size by 42%. Synergy among these agents suggests that they inhibit PMN function of distinct cellular mechanisms (as yet not elucidated). Further, early in vivo results encourage speculation that such synergy might ultimately be exploited clinically, although such speculation must presently be regarded as preliminary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00916241
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Steroids decrease granulocyte membrane fluidity, while phorbol ester increases membrane fluidity (1990)
    Springer
    Inflammation 14 (1990), S. 61-70 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract High concentrations of corticosteroids inhibit granulocyte responses and disrupt agonist receptor function. Dose-response and time-course considerations make it unlikely that these effects are mediated via the glucocorticoid receptor, a concept further supported by the ability of sex steroids to work similar effects. We postulated that steroids nonspecifically altered granulocyte membrane fluidity, which we measured directly by electron paramagnetic resonance. As predicted, methylprednisolone caused a dose-dependent increase in order parameter (decrease in fluidity) calculated on the basis of EPR spectra, using 5-doxylstearic acid (5-DS) as a probe of resting PMN membranes. This trend was highly significant (P 〈 0.001; P at 0.5 mg/ml 〈 0.01). Qualitatively similar results (but with different dose-response features) were obtained with conjugated estrogen. Granulocyte agonists (such as PMA) showed an opposite effect, which was not oxidatively mediated and which was steroid-inhibitable. 16-DS showed less prominent effects, suggesting that the membrane leaflets were more strongly affected than was the deep region of the membrane. Ibuprofen, which has similar effects to those of methylprednisolone on PMN aggregation and receptor function, caused a fluidizing rather than a stiffening of the membrane; this surprising result may indicate that there is a critical range of membrane fluidity for normal function, outside of which-in either direction-agonist receptor dysfunction occurs. We conclude that the immediate effects of very high doses of steroids are probably not mediated by corticoid receptors; instead, they may be due to changes in membrane fluidity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00914030
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  • 4
    Electronic Resource
    Electronic Resource
    Influence of dietary omega-3 fatty acids on granulocyte function (1982)
    Springer
    Inflammation 6 (1982), S. 227-234 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Manipulation of dietary fatty acid content has been shown to influence platelet aggregation responses, Because granulocytes and platelets interact in a variety of biologic systems, we wondered whether a similar effect might be observed on granulocytes. Granulocyte function was therefore studied in three donors prior to and after three weeks upon a diet supplemented with large amounts of eicosapentaenoic acid. The previously reported attenuation of platelet aggregation was observed, but no effect was seen on granulocyte aggregation, chemotaxis, or superoxide production. Although several other explanations are possible, we suggest that the most likely explanation for this dichotomy is that granulocyte aggregation and chemotaxis are not centrally dependent upon production of thromboxane A2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00916404
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  • 5
    Electronic Resource
    Electronic Resource
    Aggregation, chemotaxis, and chemiluminescence of canine granulocytes (1983)
    Springer
    Inflammation 7 (1983), S. 67-80 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Wishing to extrapolate in vitro observations of granulocyte function and pharmacology made with human cells to animal models of diseases in which we believe granulocyte stimulation to play a major role, we examined techniques for preparation of canine granulocytes and conducted a survey of the function and pharmacology of those cells. Isotonic density gradients of PercollTMproved a simple and highly satisfactory method of preparation. Canine granulocytes in most respects paralleled human cells in function and pharmacology, except that canine cells lacked receptors for formylated oligopeptides and resisted them as stimuli; canine plasma contained a heat-labile inhibitor of canine PMN aggregation, oxidative metabolism, and myeloperoxidase release; canine PMNs were not inhibited in aggregation by protease inhibitors such as aprotinin; canine response to ibuprofen and steroids was more variable than that of human cells, and synergy between those agents was less readily demonstrated; heterologous stimulation (canine cells by human C5a or vice versa) led to a different time course and maximum response from those observed in the homologous systems. Canine granulocytes were readily marked with indium-111, and functioned normally in vitro and survived well in vivo after marking. We conclude that the dog is a suitable animal for studying the role of stimulated PMNs in disease, as long as the observed differences are taken into account in experimental design and data interpretation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00918009
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  • 6
    Electronic Resource
    Electronic Resource
    Inhibition by halothane, but not by isoflurane, of oxidative response to opsonized zymosan in whole blood (1989)
    Springer
    Inflammation 13 (1989), S. 621-630 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an attempt to clarify some apparent discrepancies in reports of the effects of anesthetic agents upon granulocyte function, we studied the effects of halothane and isoflurane, using techniques that allowed us to perform the assays in whole blood and in sealed vials to prevent volatile gas evolution; assay gas concentrations were measured, rather than inferred. Chemiluminescence, superoxide production, and hydrogen peroxide production were assessed after presentation of opsonized zymosan as a phagocytic stimulus. Incubation with halothane led to a highly statistically significant dose-related inhibition of Chemiluminescence (maximum 66%), H2O2 production (67%) and ·O 2 − production (61%), within the concentration range observed in blood from patients undergoing general anesthesia. In contrast, the presence of isoflurane led to no statistically significant changes in any of the functions measured. Cells harvested from patients undergoing elective halothane anesthesia showed the same functional inhibition, but for quantitative differences likely due to the inability to control for dilution effects in clinical samples. It has been suggested that halothane anesthesia may be associated with excess mortality in septic patients; although the results we report are readily reversible, their presence during a prolonged anesthesia could be harmful in a patient who is not immunologically normal and/or who is already infected. Careful clinical trials will be necessary to determine if isoflurane is a superior agent in this context.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00914306
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  • 7
    Electronic Resource
    Electronic Resource
    Digital integration of granulocyte aggregation responses (1980)
    Springer
    Inflammation 4 (1980), S. 381-395 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pulmonary leukostasis and lung dysfunction associated with intravascular complement activation results from C5a-mediated granulocyte (GR) aggregation, a phenomenon which can be reproduced in vitro using standard nephelometric techniques. To produce a more subjective measure of the extent and rate of GR aggregation responses we added a digital integrator to the system. The validity of this approach was substantiated by the close correlation between the aggregating and chemotactic activities of C5a andN-formyl-metionine-leucine-phenylalanine. Use of this technique enabled us to define the dose-response relationship of the aggregation produced by the cationophore A23187 and the inhibitory effect of tetracaine on divalent cationdependent aggregation responses. The aggregation produced by these three stimuli does not result primarily from simple cross-linking of surface charges because, unlike the passive cell-cell association produced by the cation poly-l-lysine, it is not inhibited by anionic poly-l-glutamic acid. The importance of microtubules as regulators of GR adhesiveness was substantiated by the inhibitory effects of colchicine (but not lumicolchicine) on aggregation in this system. These data suggest that this integration of light transmission increments is a useful adjunct to this basic technique, whether used as a bioassay for chemotactic stimuli or as a model to study the many factors which regulate GR adhesiveness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00916049
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  • 8
    Electronic Resource
    Electronic Resource
    Development of a simple radioimmunoassay for human C3a (1988)
    Springer
    Inflammation 12 (1988), S. 265-276 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A radioimmunoassay was devised for the human complement cleavage product, C3a, using charcoal separation and selective precipitation of interfering substances. When compared with the commercially available immunoassay now marketed, the assay reported here was somewhat simpler to perform; furthermore, it overcame delivery and availability problems in Europe. The assay showed a mean recovery of 87% of known amounts of C3a or C3adesarginine and had a sensitivity of 32 ng C3a per milliliter of plasma; coefficients of variance were comparable to other radioimmunoassays in common use. Using this assay in a first clinical application, we were able to document a small but statistically significant rise in [C3a] during cardiopulmonary bypass.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00920078
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  • 9
    Electronic Resource
    Electronic Resource
    Inhibition of granulocyte function by steroids is not limited to corticoids (1988)
    Springer
    Inflammation 12 (1988), S. 277-284 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Noting that corticosteroid doses required for protection in shock models exceeded those required to saturate glucocorticoid receptors in mammalian cells, we postulated a nonspecific physicochemical effect of steroids upon the cell membrane, and therefore tested three noncorticoid steroids for their effects on granulocyte function. All three (conjugated equine estrogen, a synthetic progestogen, and a synthetic androgen) behaved in manner analogous to corticoids at similar concentrations, inhibiting granulocyte aggregation, chemotaxis, and chemiluminescence, as well as binding to the granulocytes of the synthetic oligopepitide agonist f-Met-Leu-Phe. Estrogen was further shown to reduce granulocyte membrane fluidity, assessed by electron paramagnetic resonance. We propose that the unique effects of extremely high-dose corticosteroids are not mediated via the glucocorticoid receptor, but result rather from physicochemical effects of the drugs upon the membranes of effector cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00920079
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  • 10
    Electronic Resource
    Electronic Resource
    Hyperacute pulmonary vasculitis in rabbits receiving prolonged infusions of activated complement (1983)
    Springer
    Inflammation 7 (1983), S. 1-13 
    Details
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have postulated a role for activated plasma complement and for stimulated granulocytes in the triggering events of the adult respiratory distress syndrome (ARDS). Because brief periods of complement activation have proved to be pale mimics of the clinical syndrome, we extended our earlier models by infusing potently activated plasma complement into rabbits over a prolonged period of time (3 h). The expected leukostasis occurred, but pulmonary dysfunction remained modest. Nonetheless, piecemeal microvascular necrosis did develop, rendering this current model more credible than former models as a mimic of triggering events in ARDS; longer-term follow-up of such animals will be necessary to determine if this is indeed the case. Perhaps of even greater interest, the neutrophilic leukostasis was observed to progress over the 3 h to a predominantly lymphocytic leukostasis, a dramatically more rapid progression than is typical of such immune complex diseases as serum sickness and the Arthus reaction; further studies are in progress to elucidate the mechanism of this lymphostasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00918003
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