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Biomedical subjects

R van Furth

Publications and source records attributed to R van Furth.

At least 235 records · Page 13Linked to original sources
PubMed1985

Relationship between extracellular stimulation of intracellular killing and oxygen-dependent microbicidal systems of monocytes.

Human monocytes require serum components immunoglobulin G, C3/C3b, and B/Bb to exert optimal microbicidal action against ingested microorganisms. The present study was performed to find out whether these factors act by enhancing oxygen-dependent antimicrobial mechanisms. Serum enhanced oxygen consumption and superoxide production by monocytes before phagocytosis, but did not further increase these processes in monocytes that had recently ingested bacteria. Furthermore, serum did not boost iodination during intracellular killing by monocytes. Phorbol myristate acetate, N-formyl-methyonyl-leucyl-phenylalanine, concanavalin A, and concanavalin A-Sephadex all stimulated the conversion of O2 to H2O2 by monocytes, but only concanavalin A augmented intracellular killing. Reactive oxygen intermediates generated by cell-free enzymes (xanthine oxidase or glucose oxidase) in concentrations comparable to those accumulating extracellularly during incubation of monocytes containing bacteria with phorbol myristate acetate did not promote intracellular killing. The presence of catalase during phagocytosis inhibited killing, but had no effect on killing in the postphagocytic state. Monocytes deprived of glucose for 24 h showed markedly impaired O2 consumption, O2- generation, and bacterial killing; all of these effects were rapidly reversed by restoration of glucose. It is concluded that both an intact respiratory burst and extracellular serum factors are necessary for optimal killing of intracellular Staphylococcus aureus by human monocytes. Serum does not appear to act by enhancing the respiratory burst, but rather to have a separate, synergistic role, the biochemical basis of which is unknown.

Cell Membrane↗
PubMed1985

Effect of bacterial competition on the opsonization, phagocytosis, and intracellular killing of microorganisms by granulocytes.

The ingestion of Escherichia coli by human granulocytes in vitro was reduced in the presence of Bacteroides fragilis or Staphylococcus aureus. This reduction of ingestion proved to be mainly attributable to the absence of opsonization of E. coli, which was due to complement consumption by B. fragilis and S. aureus. The intracellular killing of E. coli was decreased in the presence of B. fragilis and S. aureus because of consumption of complement components required for extracellular stimulation of granulocytes to kill intracellular bacteria. Decreased intracellular killing of E. coli by granulocytes containing either B. fragilis or S. aureus is due to the limited killing capacity of granulocytes. These interactions between E. coli and B. fragilis or S. aureus found for phagocytosis and intracellular killing were also observed in in vivo studies: in an experimental thigh lesion infection in mice, E. coli showed stronger proliferation after coinoculation with B. fragilis or with S. aureus than after injection of E. coli alone. These in vitro and in vivo findings indicate that bacterial interactions, not only between aerobic and anaerobic bacteria but also between two species of aerobic microorganisms, compete for host defense mechanisms (i.e., opsonization, phagocytosis, and intracellular killing).

Animals↗
PubMed1985

Opsonic activity of cord blood sera against various species of microorganism.

The results of the present study on the opsonic activity of cord blood serum against various microorganisms (Staphylococcus aureus, Escherichia coli, and group B streptococci) show that the activity of cord blood serum in promoting IgG-mediated ingestion is equal to that of sera of healthy adults. This implies that IgG concentrations, as assessed by immunochemical methods, in cord blood and adult sera represent functionally similar IgG activities. Ingestion of microorganisms involving complement-dependent opsonization was found to be of the same level for cord blood and adult sera, when the opsonization occurred via the classical pathway of complement activation. However, due to decreased concentrations of factors B, P, and D in cord blood serum, optimal opsonization of microorganisms requiring the alternative pathway of complement was impaired. Taken together, these results indicate that an opsonic defect of cord blood serum affects mainly microorganisms requiring opsonization via the alternative pathway of complement.

Blood Bactericidal Activity↗
PubMed1985

Differences in initial rate of intracellular killing of Salmonella typhimurium by resident peritoneal macrophages from various mouse strains.

To determine the underlining mechanism of the difference in innate susceptibility of mouse strains to infection by Salmonella typhimurium, the ingestion and in vitro intracellular killing of S. typhimurium by resident peritoneal macrophages of mouse strains that differ in natural resistance to this microorganism has been studied. The results revealed that the rate constants of in vitro phagocytosis (Kph) in the presence of inactivated rabbit immune serum did not differ between macrophages of susceptible C57BL/10 and resistant CBA mice (for both strains: Kph = 0.021 min-1). The rate constant of in vitro intracellular killing (Kk) was determined 1) after in vivo phagocytosis (CBA, Kk = 0.055 min-1; C57BL/10, Kk = 0.031 min-1), 2) after in vitro phagocytosis of preopsonized bacteria (CBA, Kk = 0.020 min-1; C57BL/10, Kk = 0.012 min-1), and 3) during continuous phagocytosis in vitro (CBA, Kk = 0.029 min-1; C57BL/10, Kk = 0.013 min-1). With all three approaches, the initial rate of intracellular killing by normal macrophages of Salmonella-resistant CBA mice amounted to about 1.7 times the value found for macrophages of susceptible C57BL/10 mice (p less than 0.01). This trait difference was independent of the previous way of ingestion of the bacteria, unaffected by the kind of opsonization, and specific for S. typhimurium, because Staphylococcus aureus and Listeria monocytogenes were killed by macrophages of these mouse strains with equal efficiency (p greater than 0.50). These findings indicate that a difference in genetic background expressed in the efficacy of intracellular killing by resident peritoneal macrophages immediately upon ingestion of S. typhimurium is relevant for the innate resistance of mice against S. typhimurium.

Animals↗
PubMed1985

Functions of granulocytes and monocytes in primary biliary and alcoholic cirrhosis.

Granulocytes and monocytes from patients with primary biliary cirrhosis (PBC) and alcoholic cirrhosis (AC) were investigated with respect to the major functional activities involved in host defence against micro-organisms. Chemokinesis, chemotaxis, phagocytosis, and intracellular killing of micro-organisms as well as the ability of these cells to consume O2 and convert it to H2O2 were all comparable to those of granulocytes and monocytes of healthy donors. Investigation of sera of PBC and AC patients revealed normal opsonic activity in sera from both sources and normal chemotactic activity in PBC sera. Compared with normal donor serum AC sera were less chemotactic for granulocytes but not for monocytes. This diminished chemotactic activity is probably ascribable to the presence of a specific inhibitor of granulocyte chemotaxis in AC serum. Taken together, these results indicate that a postulated defective functioning of phagocytic cells can not explain the frequent and serious infections observed in patients with chronic liver disorders.

Adult↗
PubMed1984

Chemotactic and random movement of cord-blood granulocytes.

Chemotactic responsiveness and random movement of cord-blood granulocytes were studied with a modified Boyden's method. Cord-blood granulocytes were less active chemotactically than granulocytes from healthy children and adults, whereas the random filter movement of the cells from all three sources was about the same. In cord sera, concentrations of cell directed chemotaxis inhibitors were equal to those in sera from other age groups. Compared with the situation in healthy children and adults, the generation of chemotactic factors in cord-blood sera was impaired. This impairment was not related to an increased activity of chemotactic factor inactivators. Measurement of the cyclic nucleotide levels in granulocytes from cord-blood and from children belonging to various age groups revealed that the cord granulocytes have significantly lower concentrations of cAMP and cGMP, which could have been responsible for the decreased chemotactic responsiveness.

Adult↗
PubMed1984

Dual origin of mouse spleen macrophages.

The present study concerns the isolation, characterization, origin, and kinetics of spleen macrophages. The spleen was first perfused in situ to remove monocytes from the vascular bed and then dissected and treated with collagenase. The macrophages in the cell suspension thus obtained were characterized morphologically and cytochemically and then quantitated. The spleen cell suspension was incubated for 24 h in Leighton tubes to obtain an enriched glass-adherent population of macrophages for characterization and [3H]thymidine-labeling studies. Almost all of the adhering macrophages were esterase positive, had Fc and C3b receptors, and ingested EIgG and opsonized bacteria. In vitro labeling with [3H]thymidine showed that approximately 5% of the mononuclear phagocytes in the spleen synthesize DNA and must be considered to be dividing cells. The course of the number of labeled monocytes and macrophages after a single injection of [3H]thymidine indicates migration of monocytes into the spleen, where they become macrophages. Calculation of the influx of monocytes into the spleen and of the local production of macrophages by DNA-synthesizing mononuclear phagocytes showed that under steady-state conditions, 55% of the population of spleen macrophages is supplied by monocyte influx and 45% by local production. This means that there is a dual origin of spleen macrophages. The mean turnover time calculated with the value for the efflux of spleen macrophages is 6.0 d.

Animals↗
PubMed1984

Hyperimmunoglobulinaemia D and periodic fever: a new syndrome.

Six patients of Dutch ancestry with a long history of recurrent attacks of fever of unknown cause were found to have a high serum IgD level and a large number of plasma cells with cytoplasmic IgD in the bone marrow. Because the clinical picture in some ways resembled that of familial Mediterranean fever (FMF), sera of patients with FMF were also investigated; only one of eight such patients had a raised serum IgD.

Adolescent↗
PubMed1984

Differences in the response of inbred mouse strains to the factor increasing monocytopoiesis.

Previous studies have shown that monocyte production during an inflammatory response is controlled by the factor increasing monocytopoiesis (FIM), secreted by macrophages at the site of inflammation. The inflammatory reaction to latex particles and a saline-soluble extract of Listeria monocytogenes (SEL), expressed as the number of monocytes in the circulation and of macrophages at the site of inflammation, was about twice as strong in C57BL/10 mice compared with CBA mice. This raised the question as to the mechanism underlying these differences. One possibility might be that these mouse strains differ with respect to the production of FIM, but this cannot be the case because the maximum levels of FIM activity in the serum of both C57BL/10 and CBA mice given latex or SEL intraperitoneally were almost the same; however, the courses of FIM activity in the two strains after intraperitoneal latex were not exactly synchronous. Another possibility is that the sensitivity of monocyte precursor cells for FIM differs. Evidence for the latter was provided by the finding that the intravenous injection of sera with FIM activity obtained from C57BL/10 and from CBA mice into the C57BL/10 mice evoked monocytosis, whereas CBA mice did not respond to these sera. Earlier studies showed that an increase of monocytes after the injection of serum containing FIM reflects increased monocyte production. Taken together, the results of the present study demonstrate that one of the mechanisms underlying the genetic control of the inflammatory response is, rather than enhanced FIM synthesis, the ability of monocyte precursors in the bone marrow to respond to FIM by increased monocyte production.

Acute Disease↗
PubMed1984

Correlation between opsonic activity for various microorganisms and composition of gammaglobulin preparations for intravenous use.

In this study 12 commercial immunoglobulin preparations for intravenous administration were investigated with respect to their opsonic activity for various strains of Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes, and group B streptococci, and in addition, the concentration of unsplit IgG molecules, IgG fragments, and IgG aggregates (dimers) was determined. The results show that four preparations that had been treated with enzyme or by reduction and alkylation had hardly any opsonic activity; the other preparations were as effective as inactivated serum. A statistical analysis showed an excellent correlation between the concentration of intact IgG molecules in a preparation and the opsonic activity for the various bacteria; a negative correlation between the concentration of IgG fragments and the opsonic activity was found. The combination of the two techniques used in this study provides a basis for recommendations on the choice of gammaglobulin preparations for clinical use.

Escherichia coli↗
PubMed1984

Quantification of the effect of anti-anaerobic drugs in experimental Bacteroides fragilis infection in mice.

As a basis for the quantitation of the effect of anti-anaerobic drugs in vivo, an experimental thigh infection in mice was developed in which co-inoculation of Bacteroides fragilis and Escherichia coli is obligatory for proliferation of Bact. fragilis. The inhibitory effect of metronidazole and tinidazole on the proliferation of Bact. fragilis was assessed in this model. Both metronidazole and tinidazole showed a significant dose-effect relationship with respect to the outgrowth of Bact. fragilis but not that of E. coli. The effect of both drugs on Bact. fragilis was similar and at all dosage levels a significant correlation was found between the numbers of Bact. fragilis and E. coli.

Animals↗
PubMed1984

Role of granulocytes in the prevention and therapy of experimental Streptococcus sanguis endocarditis in rabbits.

The contributions of granulocytes to the prevention and therapy of Streptococcus sanguis endocarditis with procaine benzylpenicillin (PBP) was investigated in rabbits. Depletion of granulocytes by treatment with mechlorethamine appeared to have no significant effect on either the prophylactic or therapeutic activities of PBP. Administration of 3,000 IU of PBP before inoculation with S. sanguis retarded the course of the endocarditis for only 24 h whether granulocytes were normal or depressed in numbers. Prophylaxis with either 15,000 or 30,000 IU of PBP was equally effective in non-granulocytopenic and granulocytopenic rabbits. Treatment of established infections with PBP at doses of 3,000 to 300,000 IU of PBP at 12-h intervals for 48 h was equally effective in rabbits with normal and depressed numbers of granulocytes. The effect of 3,000 IU of PBP was equivalent, however, to that of granulocytes alone, as shown by the fact that the numbers of CFU per gram of vegetation in the granulocytopenic rabbits treated with this dose of PBP and in the non-PBP-treated control rabbits were not significantly different.

Agranulocytosis↗
PubMed1984

Role of granulocytes and monocytes in experimental Escherichia coli endocarditis.

The role of granulocytes and monocytes during the induction and course of Escherichia coli endocarditis was investigated in rabbits by selectively depleting monocytes from the circulation with the drug VP16-213 and granulocytes and monocytes with nitrogen mustard. For induction, the number of E. coli needed to infect the vegetations in 50% of the rabbits was significantly lower in rabbits with combined granulocytopenia and monocytopenia than in those with selective monocytopenia or in control rabbits, whereas the number of E. coli needed to infect 50% of the rabbits did not differ between the latter two. During the course of the endocarditis in endocardial vegetations, the numbers of CFU per gram of vegetation were significantly higher in the rabbits with combined granulocytopenia and monocytopenia than in the monocytopenic and control rabbits but did not differ between the latter two. The numbers of granulocytes in the circulation and the numbers of CFU per gram of vegetation showed a significant negative correlation that was not measurably influenced by the duration of the disease but was dependent on the number of E. coli injected for the induction of endocarditis. Granulocytes were found to be most effective at the lowest numbers of bacteria injected. In the circulation, too, the numbers of CFU per milliliter were significantly higher in rabbits with combined granulocytopenia and monocytopenia than in those with selective monocytopenia and control rabbits, and there was a significant negative correlation between the numbers of granulocytes and CFU per milliliter of blood. From these findings we conclude that granulocytes play a protective role during the induction and course of E. coli endocarditis in rabbits, whereas no role is demonstrable for monocytes.

Animals↗
PubMed1984

Effect of thioglycolate on phagocytic and microbicidal activities of peritoneal macrophages.

Brewer thioglycolate-elicited mouse peritoneal macrophages were as active as resident peritoneal macrophages in the phagocytosis of opsonized Staphylococcus epidermidis but were unable to kill ingested microorganisms. This decreased functional activity was restricted to Brewer thioglycolate-elicited macrophages, since peritoneal macrophages elicited with NIH thioglycolate, alone or supplemented with agar and methylene blue, were as active as resident peritoneal macrophages. No effect of agar on the functional activities of macrophages was observed. A defective intracellular killing by peritoneal macrophages due to Brewer thioglycolate was seen only after an intraperitoneal injection with thioglycolate, not after in vitro incubation of resident macrophages with thioglycolate. The results of this study show that, depending on the kind of thioglycolate used, the functional characteristics of elicited macrophages may alter. However, none of the forms of thioglycolate investigated induced the recruitment of activated macrophages.

Animals↗
PubMed1984

Extracellular stimulation by serum proteins required for maximal intracellular killing of microorganisms by mouse peritoneal macrophages.

Intracellular killing of catalase-positive Staphylococcus aureus by resident mouse peritoneal macrophages was very low in the absence of serum but maximal in the presence of fresh normal serum. A large proportion of catalase-negative Streptococcus pyogenes were killed in the absence of extracellular serum, and maximal killing was reached only when serum was present extracellularly. Further investigations revealed that stimulation of intracellular killing by extracellular serum is dependent on the interaction of immunoglobulin G and Fc receptors and of complement component C3b with C3b receptors in the macrophage membrane.

Animals↗
PubMed1984

Characteristics and functional capacities of human cord blood granulocytes and monocytes.

Cord blood phagocytic cells were characterized with respect to cytochemical activities, Fc gamma and C3b receptors, and capacity to phagocytose and kill various species of bacteria. The percentages of peroxidase-positive granulocytes and monocytes from neonates and adults were comparable; the percentage of esterase-positive cord-blood monocytes was about two-thirds of that of adults' blood monocytes. The numbers of cord blood and adults' monocytes with Fc gamma and C3b receptors were similar. Phagocytic and intracellular killing capacities of cord blood granulocytes and monocytes were investigated for Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes, and group B Streptococcus type III. The rates of phagocytosis and intracellular killing by granulocytes from newborns proved to be comparable to the corresponding values for granulocytes from adults. Cord blood monocytes phagocytosed E. coli, S. aureus, and S. pyogenes at a normal rate, and killed ingested E. coli and S. pyogenes intracellularly at the same rate as adults' monocytes did. However, S. aureus was killed at a much lower rate by cord blood monocytes than by monocytes from adults. Phagocytic activity for group B Streptococcus was impaired and killing of these bacteria by cord blood monocytes was virtually nil. The latter finding might partially explain the frequent streptococcal infections in newborns.

Adult↗
PubMed1984

Role of granulocytes in the induction of an experimental endocarditis with a dextran-producing Streptococcus sanguis and its dextran-negative mutant.

The role of granulocytes in the induction of endocarditis with a dextran-producing Streptococcus sanguis and a dextran-negative mutant of this strain was studied. The number of colony-forming units of Streptococcus sanguis needed to colonize the vegetations in 50% of the rabbits (ID50) was significantly lower for the parent strain than for the dextran-negative mutant. However, in granulocytopenic rabbits the ID50s of both strains did not differ measurably. Dextran-negative streptococci were more readily cleared from the circulation than dextran-positive, but in this respect no difference was found between control and granulocytopenic rabbits, which indicates that clearance cannot account for the difference in ID50 between the two strains in the control group. At serum concentrations of 5% and lower, in-vitro granulocytes phagocytosed the dextran-negative streptococci more rapidly than the dextran-positive. The intracellular killing of the streptococci was no influenced by dextran production. This study suggests that an impaired phagocytic removal of attached bacteria from the vegetational surface can be a factor promoting the induction of endocarditis by dextran-producing streptococci.

Animals↗