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[Features of the metabolic activity of the mononuclear phagocytic system in multiple sclerosis patients].

Metabolic activity of the mononuclear phagocytic system (MPS) was studied in 65 patients with disseminated sclerosis (DS) and 65 control persons by determination of the test-substance biotransformation intensity. Sulfadimezine undergoing acetylation in MPS cells was chosen as a test-substance. Sulfadimezine was administered per os; both unchanged drug and its acetylated metabolite were detected in urine in 6 hours. Correlation between acetylated and non-acetylated sulfadimezine levels permitted dividing the examinees into "rapid" or "slow" acetylators (inactivators). Patients with DS belong mainly to slow acetylators since the test-substance in MPS cells of these patients is inactivated slowly. Correlation between "slow" and "rapid" acetylators in patients with DS was 5:1, that in the control group 2:1. A similar pattern was reported previously in patient with systemic lupus erythematosus. New approaches to the mechanisms of DS development based on MPS functions analysis are outlined.

Acetylation↗

An animal model of alloimmune thrombocytopenia. I. The role of the mononuclear phagocytic system (MPS).

To understand better the role of the mononuclear phagocytic system (MPS) in accelerated destruction of donor platelets in man following repeated platelet transfusions, an experimental model has been developed using genetically defined animals. Brown Norway rats were immunized with Lewis platelets. Antibodies were detected by immunofluorescence microscopy, and their effects demonstrated by 111In-labeled platelet clearances in vivo and by measurements of organ radioactivity in sacrificed animals. All immunized rats developed platelet alloantibodies and showed a significant decrease (P less than 0.001) in donor platelet survival with sequestration in both the liver and spleen. Liver to spleen radioactivity ratios in nonimmunized animals were less than 0.1, whereas immunized animals had a ratio between 0.6 and 1.0, indicating relatively greater hepatic clearance of allogenic platelets. Studies currently in progress on the administration of vinca alkaloids to immunized animals suggest that the MPS can be impaired from clearing allogenic platelets. This model, therefore, should be helpful in studying the role of the MPS in platelet destruction.

Animals↗

Modulation of mononuclear phagocyte system function and circulating immune complexes by lyophilized concentrates in patients with classic hemophilia.

Infusions of lyophilized antihemophilic factor concentrates in patients with hemophilia were found to affect both circulating immune complexes and in vivo mononuclear phagocyte system function. Following infusion nine patients had simultaneous assessment of serial immune complex levels and mononuclear phagocyte system clearance of IgG-sensitized autologous erythrocytes relative to a previously established baseline. Nine patients also had a separate second sequence, and two a third sequence, of serial immune complex measurements in relation to infusions. The net change in immune complexes over the 2- to 4-hr interval following infusion was consistent in 10 of 11 study pairs (P less than 0.01) despite different antihemophilic factor preparations for each study and different individual patient responses. This change could not be explained by immunochemical rearrangement in infusate and serum since in vitro mixing experiments showed no relationship to in vivo results. Change in mononuclear phagocyte system function showed a strong correlation with change in complexes (r = 0.70; P less than 0.05). It is suggested that infusions of antihemophilic factor can modulate the mononuclear phagocyte system which in turn alters immune complex levels. Both of these effects could potentially influence immune regulation which has been shown to be abnormal in other hemophiliac patient groups.

Adolescent↗

Effects on the murine mononuclear phagocyte system of chronic administration of liposomes containing cytotoxic drug or lipid A compared with empty liposomes.

In experiments designed to examine the adverse effects of chronic liposome administration in vivo on the mononuclear phagocyte system (reticuloendothelial system), the presence of drug entrapped in the liposomes may increase the level of reticuloendothelial impairment. We have compared the effects on the mononuclear phagocyte system in mice of chronic administration of empty liposomes with the effects of liposomes containing the anti-leishmanial drug meglumine antimoniate. We have also examined the effect on the mononuclear phagocyte system of continued injections of liposomes containing lipid A, a component of bacterial lipopolysaccharide, which is responsible for macrophage activation. Ten intravenous injections of multilamellar liposomes composed of dipalmitoylphosphatidylcholine and cholesterol (1:0.75 M ratio) were given to ICR mice over a 25-day period. Two individual groups of mice received endotoxin-free liposomes in which meglumine antimoniate was either present or absent. One addition group received liposomes containing lipid A derived from Escherichia coli lipopolysaccharide. A control group received sterile saline injections. In each group, a depression of the phagocytic index, as measured by reduction of uptake of particulate carbon, was observed among some of the individual animals 24 h after the first injection. In many mice a marked splenomegaly was observed. A depressed phagocytic index and splenomegaly were most marked for mice receiving lipid A liposomes. However, there was a large individual variability among mice receiving these preparations and some mice in each group had normal spleen size and a nearly normal phagocytic index. Tissue distribution of liposomes containing [14C]dipalmitoylphosphatidylcholine as a phospholipid marker was examined in all groups in mice 24 h after the last injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mononuclear phagocytic system in acute pancreatitis.

1. Functional alterations of the mononuclear phagocytic system (MPS) may be an important factor in the pathogenesis of infection in acute pancreatitis (AP). In the present study, MPS activity was investigated in rats and hepatic blood flow (HBF) was also determined. 2. A total of 122 male Wistar rats were divided into three groups: 1, AP group (N = 51); 2, sham-operated (SO) (N = 49); 3, intact group (IG) (N = 22). AP was induced by retrograde injection of 0.5 ml of 2.5% sodium taurocholate saline into the main biliopancreatic duct under ketamine chloride anesthesia. SO animals were submitted to the same surgical steps as AP animals except for AP induction. 3. Each experimental group was subdivided into two subgroups. The first subgroup was submitted to the study of MPS activity as follows: each group was injected with colloidal 198Au and liver clearance parameters were determined 2 h (N = 11), 12 h (N = 10) and 24 h (N = 10) later in the AP group, and 2 h (N = 9), 12 h (N = 10) and 24 h (N = 11) later in the SO group. In the second subgroup, HBF was assessed using 131I-bromosulphalein at 2 h (N = 10) and 24 h (N = 10) in the AP group and at 2 h (N = 10) and 24 h (N = 10) in the SO group. The IG was submitted to both radioactive tracer studies. Each animal was used for only one experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Impairment of the murine mononuclear phagocyte system function by antigenic stimulation.

This study examined the mononuclear phagocyte system (MPS) capacity to eliminate IgG-sensitized syngeneic erythrocytes (EA) after antigenic challenge. Survival data of EA in normal and preimmunized mice showed that a single dose of T-dependent antigen was able to delay Fc gamma R-dependent clearance. This impairment in EA elimination was dependent on the dose of antigen injected. On the other hand, T-independent antigens, B cell mitogen, and the inflammatory agent Freund's incomplete adjuvant were ineffective in modulating MPS function. As expected, the liver and the spleen were the main sites of EA trapping, but the spleen of immunized mice sequestered significantly less EA than that of control mice. Impaired clearance capacity was observed as soon as 24 hr after immunization and was persistent up to the seventh day after antigenic stimulation. Moreover, mice decomplementation by cobra venom factor treatment did not prevent the impairment of MPS by antigenic stimulation, suggesting that it is strictly Fc gamma R dependent. Our results indicate that stimulation of the immune system by T-dependent antigens can diminish the Fc gamma R-mediated clearance capacity of the MPS. The possible mechanisms involved in this regulation are discussed.

Animals↗

Influence of deoxyspergualin on mononuclear phagocytic system in mice.

The influence of deoxyspergualin (DSG) on mononuclear phagocytic system was examined in BALB/c mice. DSG did not influence on both the organ distribution of sheep red blood cells (SRBC) and blood clearance of colloidal carbon when the agent was administered intraperitoneally into mice at doses of 5.0 and 10.0 mg/kg for six consecutive days before antigen. Hemagglutination titers in experimental and control mice did not differ significantly when 10.0 mg/kg of DSG was given six times before SRBC injection. However, when administered during the course of the response (days 0 to 5) DSG (5.0 mg/kg/day) markedly suppressed antibody formation.

Animals↗

In vivo clearance by the mononuclear phagocyte system in humans: an overview of methods and their interpretation.

The mononuclear phagocyte system (MPS) is responsible for the elimination of foreign material, effete autologous material and immune complexes. To study the relationship between MPS function and human disease, several test substances have been developed, and used to determine the clearance capacity of the MPS in human subjects in vivo. These test substances and the multitude of factors that influence the elimination of these substances (and complicate the interpretation of the test results) are discussed. Use of these probes has provided important new insights, that may lead to the development of treatment modalities by which MPS function is modified in order to influence disease processes more effectively.

History, 20th Century↗

[Use of liposomes to demonstrate the function of the mononuclear phagocyte system].

The possibility of using liposomes containing an indicator composition (dye or fluorophor) for the determination of the eliminative activity of the system of mononuclear phagocytes (SMP) was studied. Liposomes were obtained by the sonication of the suspension of lecithin, cholesterol and an indicator substance. The rate of the elimination of liposomes from the blood stream after their intravenous injection into Wistar rats (males) was evaluated photometrically or fluorometrically in hemolyzed blood samples taken from the animals at different periods after the injection. The data thus obtained were processed by means of a microcomputer with the use of a specially developed program. The results of this investigation suggest that liposomes can be used for the study of the eliminative activity of SMP.

Animals↗

Alterations in the lymphocytic and mononuclear phagocytic systems of turkey poults associated with exposure to poult enteritis and mortality syndrome.

In vivo and in vitro mononuclear phagocytic system functions, expression of lymphocyte subset cell surface markers in the thymus and bursa of Fabricius, and lymphocyte subset dynamics during the course of poult enteritis and mortality syndrome (PEMS) were examined. PEMS is an acute, transmissible, infectious intestinal disease accompanied by high mortality and morbidity. The etiology of this multifactorial disease remains to be elucidated; however, turkey coronavirus was initially assumed to be one of the primary agents involved. Further investigation demonstrated that turkey coronavirus was not always detectable in poults exhibiting PEMS symptoms, and, thus, PEMS poults began to be identified as positive or negative for turkey coronavirus. In each trial, uninfected hatchmate controls were compared with turkey poults that were contact exposed to PEMS poults at 7 days of age. Following intravenous inoculation, control poults cleared Escherichia coli from their circulation by 60 min, whereas viable E. coli were still present in the circulation of PEMS poults at 60 min postinoculation. Inflammatory response measured by Sephadex-elicited abdominal exudate cell recruitment and the adherence potential of abdominal exudate cells was not significantly different between uninfected and PEMS poults. The percentage of glass-adherent abdominal exudate macrophages was higher in PEMS poults. However, the ability of these macrophages to phagocytize sheep red blood cells and the average number of sheep red blood cells per phagocytic macrophage were both lower compared with uninfected controls. CD4+ expression in thymic tissue of PEMS poults at 9 days postinfection was significantly lower. The CD4+:CD8+ lymphocyte ratio in peripheral blood leukocytes from coronavirus-negative PEMS poults was lower than that from both uninfected and coronavirus-positive PEMS poults at 14 days postinfection. In the spleen, the CD4+:CD8+ lymphocyte ratio was higher in coronavirus-positive PEMS poults as compared with the other treatments. In conclusion, immune system dysfunction in PEMS is associated with impaired mononuclear phagocytic system function and alterations in lymphocyte populations.

Animals↗

Labelling of cells of the mononuclear phagocyte system in routinely processed archival biopsy specimens with monoclonal antibody EBM/11.

When first reported, EBM/11 reacted with mononuclear phagocyte system cells only in fresh frozen sections, but it has been shown to have similar cellular specificity in routine formalin fixed, paraffin wax embedded tissue. This was achieved by limited proteolysis with protease XIV before immunocytochemical staining. In archival biopsy specimens EBM/11 produced granular cytoplasmic staining of alveolar macrophages, Kupffer cells, tingible body macrophages and sinus histiocytes, cells of splenic cords, cortical and medullary macrophages of thymus; blood monocytes, peritoneal and mesothelial macrophages; bone marrow mononuclear cells, megakaryocytes and osteoclasts; lamina propria macrophages in the gastrointestinal tract, and connective tissue cells (presumptive macrophages) of thyroid, gall bladder, skin, pancreas, ovary, myometrium, endometrium, cervix, kidney, prostate, placenta, myocardium and breast. Unlike other anti-macrophage antibodies, EBM/11 did not react with granulocytes, lymphocytes, plasma cells, platelets, endothelial and epithelial cells in paraffin wax sections. It did not label skin Langerhans' cells, microglial cells, and interdigitating reticulum cells (as in frozen sections). This study opens a new area for the specific identification by EBM/11 of mononuclear phagocyte system cells in archival biopsy specimens. It also raises the possibility that some monoclonal antibodies, believed to be reactive only in frozen sections, may react in archival tissue after limited proteolysis with an appropriate enzyme.

Antibodies, Monoclonal↗

[Functional-metabolic activity of the mononuclear phagocyte system of the blood, liver, spleen and skin in children with hepatitis B].

A total of 102 children aged 5 to 14 years with virus hepatitis B were examined for the status of the mononuclear phagocytic system in accordance with the absolute monocyte count in the circulating blood, esterase and acid phosphatase activity in the monocytes, for function of organ macrophages of the liver and spleen using dynamic scintigraphy with TC-colloid and for macrophages of the skin by the "skin window" method. The rise of the absolute count and lowering of the functional and metabolic activity of blood monocytes were directly proportional to the gravity of virus hepatitis B. The changes persisted for a long time, namely up to 1.5 to 3 months since the disease onset. There was a progressive drop of the functional activity of Kupffer cells in the liver with a maximum decrease seen within 4 to 6 weeks since the disease onset, followed by returning to normal in cyclic disease and preservation of the changes in lingering and chronic virus hepatitis B. Spleen macrophages play an active compensatory role, maintaining normal "purifying" function of the mononuclear phagocytic system. That compensatory response tension appeared high in lingering and especially in chronic virus hepatitis and may serve as a criterion for process chronicity. The changes in the mononuclear phagocytic system observed in cyclic course of mild and medium-gravity virus hepatitis B may be regarded as normal adaptive reaction and do not require any drug correction. The latter one may only be indicated in patients with grave, lingering or chronic disease patterns associated with break down or depletion of the adaptive mechanisms of the system in question.

Acid Phosphatase↗

In vivo studies on the mononuclear phagocyte system Fc receptor function in rheumatoid arthritis. Correlations with clinical and immunological variables.

The mononuclear phagocyte system Fc receptor function was assessed in 13 control subjects and 17 patients with rheumatoid arthritis (RA) by intravenous injection of IgG coated (IgG-RBC) or of heat-damaged (HD-RBC) 99mTc-labeled autologous erythrocytes. Although the clearance half-times of control and RA erythrocytes were not significantly different, the spleen to liver uptake ratios per surface area (S/Ls), determined by quantitative scintigraphic analysis, were significantly lower in RA patients than in controls. The S/Ls were significantly correlated with the Steinbrocker stages (r = 0.92; p less than 0.01), the disease duration (r = 0.73; p less than 0.01) and the total immunoglobulin levels (r = 0.73; p less than 0.01). The Clq binding activity of the sera was inversely correlated with the spleen (r = 0.90; p less than 0.01) and liver uptakes (r = 0.73; p less than 0.02). Our results therefore show an alteration of the Fc receptor function of splenic and hepatic mononuclear phagocytes in RA patients.

Adult↗

Mononuclear phagocyte system Fc-receptor function in patients with seropositive rheumatoid arthritis.

Mononuclear phagocyte system (MPS) Fc-receptor function in 20 patients with seropositive rheumatoid arthritis (RA) was investigated using radiolabelled autologous erythrocytes coated with an average of 5,800 molecules of anti-rhesus IgG (E. IgG). Although clearance times (T1/2) of E. IgG tended to be longer in RA patients than those in healthy controls (46 +/- 6 min vs 38 +/- 5 min, mean +/- s.e.m., P = 0.38), this did not reach statistical significance. Liver spleen uptake ratios (LS ratios) were increased in patients with RA (13/100 +/- 1/100 vs 7/100 +/- 1/100, P less than 0.05). There was no correlation of T1/2 or LS ratios with articular disease activity, vasculitis, ESR, IgM containing immune complex levels or Clq-binding immune complex levels. Although Clq-binding immune complex levels were significantly higher in patients with vasculitis than in those without (P less than 0.01), T1/2 and LS ratios did not differ in these two groups of patients. The T1/2 and LS ratios of E.IgG did not reveal a defect in MPS Fc-receptor function and did not correlate with one of the above-mentioned clinical and immunological parameters. We suggest that in order to establish a possible defect in Fc-receptor function correlating with disease activity and immune complex levels in RA patients, soluble immune complexes or immune complex-like material should be used as probes.

Adult↗

[Immunosuppressant effect of hydrocortisone during blockade of the mononuclear phagocytizing system].

The effect of hydrocortisone under conditions of blockade of the mononuclear phagocyte system (MPS) on antibody response in mice has been studied. The injection of hydrocortisone 4 and 48 hours before SRBC immunization suppressed humoral immune response. No increase in the suppression of immune response was observed after the injection of hydrocortisone under condition of MPS blockade. Hydrocortisone is supposed to affect, at least under the given experimental conditions, the macrophage stage of immunogenesis.

Animals↗

Role of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS).

This review describes current understanding of the role of cells of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS). Monocyte-macrophage like cells have been shown to harbor human immunodeficiency virus type 1 (HIV-I) infection in both peripheral blood and bone marrow as well as in target organs such as brain, lungs, lymph nodes, and skin. Mononuclear phagocytes that have been infected by HIV-I do not undergo significant cytopathic changes, suggesting that they may be important viral reservoirs. These and related cells may also promote the slow, persistent nature of HIV-I infections by escaping host immunologic surveillance mechanisms. There is evidence that HIV-I infections in monocytes and premonocytes can initially be latent but progress to an active viral replication state upon differentiation and/or maturation. Functional abnormalities in the mononuclear phagocyte system following infection by HIV-I have also been described, and these may be partially responsible for the severe immunosuppression characteristic of AIDS and AIDS-related disorders. These defects may be mediated by quantitative and qualitative changes in the T-helper population. Although the role of mononuclear phagocytes as viral reservoirs and as mediators of immunosuppression is still largely speculative, increasing evidence suggests that these cells influence the course of HIV-I infections.

Acquired Immunodeficiency Syndrome↗

Tumours of the mononuclear phagocyte system: a review of clinical and pathological features.

Cells of the mononuclear-phagocyte system (MPS) may give rise to a wide variety of tumours of diverse morphology ranging from acute leukemia to small benign tumours of the skin. This review of tumours of the MPS was prompted by recent advances in understanding of tumour morphology and immunologic features. It is now possible to differentiate tumours of the MPS mor precisely from tumours of lymphoid origin with which they have often been confused; however, controversy still exists as to the origin of the malignant cell of Hodgkin disease. Current evidence is reviewed which favours the view tht the malignant cell of Hodgkin disease is of monocyte origin. A classification of MPS tumours based on organ system of origin and disease extent is presented.

Adult↗