Phagocytic Activity Of Peritoneal Macrophages Research Articles

Aberrant Adherence of Peritoneal Macrophages in Endometriosis

Objectives: While retrograde menstruation occurs in most women, only some women develop endometriosis. Under normal conditions the phagocytic activity of peritoneal macrophages (PM) clears this body cavity of foreign cells while activation of PM causes secretion of biologically active substances that control inflammation. Women with endometriosis have elevated numbers of activated PM in their peritoneal fluid, yet the ectopic endometrial cells escape immune destruction. It is unclear why ectopic endometrial cells in women with endometriosis are significantly more resistant to PM-mediated phagocytosis or if these PM have a decreased capacity to mediate cytolysis of the misplaced endometrial cells. Endometriotic lesions produce haptoglobin (Hp), which in certain inflammatory states, has been shown to be immunomodulatory. Hence, this study evaluated the effects of Hp on PM attachment, the first step in phagocytosis, in women with and without endometriosis.

Immunoprotective Effect of Cu/Zn Superoxide Dismutase on Myeloid Graffi Tumor-Bearing Hamsters

Abstract Investigation on the immunoprotective activity of Cu/Zn superoxide dismutase from Humicola lutea 103 AL (HLSOD) in hamsters with transplanted myeloid tumor was performed. Survivability, tumor growth and tumor transplantability were followed. The immune status of tumor-bearing animals, injected with the optimal protective HLSOD dose, was examined during 27 days after tumor transplantation by the following parameters: (i) the number, migration and phagocytic activity of peritoneal macrophages, (ii) the phagocytic activity of blood polymorphonuclear leukocytes (PMNs), (iii) the responsibility in vitro of spleen lymphocytes to T and B cell mitogens. It was established that intraperitoneal inoculation of HLSOD produced a protective effect on the development of tumors. Elongation of the latent time for tumor appearance and inhibition of the tumor growth were observed. The decreased percentage of mortality in early stage of tumor progression was established. Immunological studies on tumor-bearing hamsters (TBH) induced a tem porary immunorestoring effect on the suppressed phagocytic activities of peritoneal macrophages and blood PMNs during the first 14 days of tumor development. Moreover, HLSOD showed an expressed stimulating effect on proliferative activity in vitro of spleen B lymphocytes from healthy and TBH as well. The immunorestoring and protective effect of the enzyme was probably due to improve of the oxidant-antioxidant balance in peritoneal phagocytes. The tem porary character of the effect can be explained with the interference of immunosuppressing factors produced by tumor tissue as well as by the presence of tumor antigens, tumor cells and antigen-antibody complexes in the circulation.

Immunotoxicity Evaluation of Resorcinol Bis-Diphenylphosphate (Fyrolflex RDP) in B6C3F1 Mice

RDP was administered daily to groups of female B6C3F1 mice by oral gavage for 28 days at dose levels of 500, 1500, or 5000 mg/kg/day body weight (BW). Control animals were sham dosed. Animals were euthanized 1 day following final exposure or following a 60-day recovery period. End point observations included necropsy and histopathology, spleen and thymus weights and cellularity, peritoneal cell numbers and differential cell analysis, splenic natural killer (NK) cell activity, lymphocyte blastogenesis, antibody-forming cell (AFC) response, peritoneal macrophage phagocytic activity, and host susceptibility to Listeria monocytogenes infection. In-life observations included weekly clinical examinations and body weights. No adverse clinical signs were noted and the only significant finding was an increase in body weight in high dose mice on week 4 as compared to sham controls. Small changes in body weight gain were seen in all dose groups as compared to sham controls after completion of dosing on weeks 5 and 6 and in mid-dose mice on weeks 7 and 12. No significant differences were found in spleen and thymus weights or in cellularity. No changes were found in peritoneal cell numbers or cell types, peritoneal macrophage phagocytic activity, or host susceptibility to infection. Likewise, splenic NK cell activity, lymphocyte blastogenesis, and AFC function were also unaffected. No histopathologic changes were observed. All animals that received positive-control substances demonstrated a significant effect in the respective tests. In conclusion, a standardized and validated battery of immune function tests demonstrated no immunotoxicity following daily oral exposure to up to 5000 mg/kg BW of RDP for 28 days.

Immunomodulatory activity of Withania somnifera

Administration of an extract from the powdered root of the plant Withania somnifera was found to stimulate immunological activity in Babl/c mice. Treatment with five doses of Withania root extract (20 mg/dose/animal; i.p.) was found to enhance the total WBC count (17 125 cells/mm 3) on 10th day. Bone marrow cellularity (27×10 6 cells/femur) as well as α-esterase positive cell number (1800/4000 cells) also increased significantly ( P<0.001) after the administration of Withania extract. Treatment with Withania extract along with the antigen (SRBC) produced an enhancement in the circulating antibody titre and the number of plaque forming cells (PFC) in the spleen. Maximum number of PFC (985 PFC/10 6 spleen cells) was obtained on the fourth day. Withania extract inhibited delayed type hypersentivity reaction in mice (Mantoux test). Administration of Withania extract also showed an enhancement in phagocytic activity of peritoneal macrophages (76.5 pigmented cells/200) when compared to control (31.5/200 cells) in mice. These results confirm the immunomodulatory activity of W. somnifera extract, which is a known immunomodulator in indigenous medicine.

Studies on the influence of a Se-restricted diet on the effects of long-term increased copper intake in guinea pigs

Guinea pigs were exposed to Se-restriction/deficiency in combination with drinking water containing 200 or 300 mg Cu/l for 6-30 weeks. Under the influence of Se-restriction/deficiency Cu excretion by bile was diminished, the Cu content of the kidneys was increased and disturbances of liver function were seen in animals exposed for prolonged periods. Some parameters of the immune system, such as the phagocytic activity of peritoneal macrophages, mitogenicity of spleen lymphocytes and the amount of lymphatic spleen tissue were also adversely affected. These effects correlated in part with the liver damage and the copper content of the kidneys. Conclusion are drawn with respect to the Idiopathic Copper Toxicosis/Indian Childhood Cirrhosis.

Low phagocytic activity of resident peritoneal macrophages in diabetic mice: relevance to the formation of advanced glycation end products.

Formation of advanced glycation end products (AGEs) is accelerated in diabetic subjects along with hyperglycemia. Although several lines of evidence indicate that AGEs stimulate macrophages to secrete several cytokines and growth factors, little is known about the effect of AGEs on the primary function of macrophages, such as phagocytosis. On the other hand, impairment of the phagocytic function of monocytes/macrophages is suggested to contribute to the low resistance to infection in diabetic subjects. In the present study, we examined the effect of AGEs on the phagocytic function of macrophages. Using flow cytometric analysis of mouse resident peritoneal macrophages, we showed that AGEs suppress phagocytosis of fluorescent microspheres by cultured macrophages. In addition, experiments using streptozotocin-induced diabetic mice demonstrated a significant decrease in the phagocytic activity of resident peritoneal macrophages 12 weeks after induction of diabetes compared with age-matched control mice. The phagocytic activity of peritoneal macrophages correlated inversely with AGE content in the adjacent peritoneal tissue. Furthermore, reduced phagocytic activity of macrophages was associated with a reduction in intracellular ATP content. Because phagocytosis is an important component of the defense system, suppression of such activity by AGEs may explain, at least in part, the increased susceptibility of diabetic patients to infection.

Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.

Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential. The whole, aqueous, standardized extracts of selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis, Withania somnifera, Piper longum and Terminalia chebula) were administered orally to experimental animals, in a dose extrapolated from the human dose, following which they were exposed to a variety of biological, physical and chemical stressors. These plants were found to offer protection against these stressors, as judged by using markers of stress responses and objective parameters for stress manifestations. Using a model of cisplatin induced alterations in gastrointestinal motility, the ability of these plants to exert a normalizing effect, irrespective of direction of pathological change was tested. All the plants reversed the effects of cisplatin on gastric emptying, while Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced intestinal hypermotility. Tinospora cordifolia was also tested for its ability to modulate the changes occurring in the phagocytic activity of peritoneal macrophages after exposure of rats to either carbon tetrachloride or horse serum. It was found to normalize the phagocytic function irrespective to the direction of change, complying to the definition of an adaptogen. All the plant drugs were found to be safe in both acute and subacute toxicity studies. Studies on the mechanisms of action of the plants revealed that they all produced immunostimulation. The protection offered by Tinospora cordifolia against stress induced gastric mucosal damage was lost if macrophage activity was blocked. Emblica officinalis strengthened the defence mechanisms against free radical damage induced during stress. The effect of Emblica officinalis appeared to depend on the ability of target tissues to synthesize prostaglandins. Recent data obtained with Tinospora cordifolia suggest that it may induce genotypic adaptation, further opening the arena for more research and experimentation.

Role of platelet activating factor in regulation of phagocytic function of macrophages in different organs

Platelet activating factor diminished phagocytic activity of peritoneal macrophages (desensitizing effect) and stimulates it in splenic macrophages (priming effect). Homologous endogenous transfer factor primed resident macrophages to subsequent exposure to platelet activating factor, while heterologous factor desensitized them. Thus, desensitization effect caused by transfer factor observed after lipopolysaccharide injectionin vivo was due to mutual effects of peritoneal and splenic macrophage populations. Therefore, an organism surviving after lipopolysaccharide injection possesses mechanisms limiting uncontrolled stimulation of macrophage function. These mechanisms are realized by down-regulation of macrophage populations by heterologous transfer factors.

Effects of concurrently administered copper and mercury on phagocytic cell activity and antibody levels in guinea pigs with experimental ascariasis

The subchronic effect of copper and mercury on selected immunological parameters in guinea pigs with experimental ascariasis was studied. Cupric sulphate and mercuric chloride administered for 28 days did not suppress the levels of specific circulating antibody in a subsequent Ascaris suum infection. Intoxication of animals significantly inhibited the phagocytic activity of peritoneal macrophages throughout the experiment. Ascaris suum infection elevated macrophage phagocytic activity but values remained significantly lower in comparison with infected non-intoxicated animals. Both the concurrently administered metal compounds changed the phagocytic ability of polymorphonuclear leucocytes in the blood. The intensity of infection assessed by the number of Ascaris larvae migrating in the lungs of animals currently intoxicated with both the metal compounds increased by 28.6%, compared with controls.

Effect of praziquantel and liposome-incorporated praziquantel on peritoneal macrophage activation in mice infected with Mesocestoides corti tetrathyridia (Cestoda).

The activation of peritoneal macrophage effector functions after therapy with free PZQ and PZQ incorporated in liposomes (lip.PZQ) was studied in the Mesocestoides corti-mouse model system. Each drug formulation was administered to an infected group of mice in 6 daily doses from day 14 p.i. Phagocytic activity of macrophages increased significantly after the administration of both drug formulations, more after lip.PZQ with an earlier peak observed for PZQ (day 3) than for lip.PZQ (day 6). Empty liposomes had no significant effect. The average counts of ingested particles in phagocytosing cells were significantly higher only after lip.PZQ administration. The pattern of changes in phagocytic activity correlated with the reduction of parasite numbers in the peritoneal cavity, with the highest observed on day 6 after therapy with lip.PZQ. Phagocytosis of lip.PZQ in vivo stimulated significantly the respiratory burst in peritoneal macrophages, with the highest concentration of superoxide anions recorded on day 1 after the last dose, whereas therapy with PZQ itself did not increase this process significantly. The capacity for the respiratory burst declined in all groups with progressing infection. It is proposed that the phagocytic activity of peritoneal macrophages after therapy was stimulated indirectly as a consequence of activation of the specific immune response. The larvicidal effect of lip.PZQ on the tetrathyridia in the peritoneal cavity was synergistic with the phagocytic activity and might be the result of double action of drug and superoxide anions generated during the respiratory burst stimulated by this drug formulation.

Comparative study on the immunological activity of a series of isoquinoline alkaloids

A series of eight isoquinoline alkaloids were isolated from Glaucium flavum or synthesized and subsequently their immunological activity was evaluated. The structure-effect relationships were evaluated in the following in vitro tests : complement activation, phagocytosis and antibody synthesis. Oxoglaucine caused significant inhibition of classical complement activity. Representatives with two phenolic hydroxyl groups decreased the phagocytic activity of peritoneal macrophages. All substances tested possessed suppressive effects on antibody synthesis against sheep red blood cells. Oxoglaucine was the most potent of the series.

A study of the role of corticosterone as a mediator in exercise-induced stimulation of murine macrophage phagocytosis.

1. It is generally accepted that physical activity provokes changes in the immune system. Previous studies have demonstrated that the stress of physical activity (swimming until exhaustion) increases the phagocytic activity of peritoneal macrophages. However, the precise mechanisms remain unknown. 2. Two experiments were performed in the present study. (A) Peritoneal macrophages from control mice were incubated with plasma from three different groups of mice: (1) mice subjected to swimming until exhaustion with no previous training, (2) mice subjected to the same activity but with 1 month of training (30 min day-1), and (3) a control (non-exercised) group. The differences in the resulting phagocytic (attachment and ingestion) capacity were measured. (B) Changes in the concentration of plasma corticosterone after exercise were also measured, and the effect of incubation with the postexercise plasma corticosterone level on the phagocytic activity of peritoneal macrophages was then studied in vitro. 3. The results were: (A) incubation with plasma from both groups of exercised mice (with and without previous training) led to increased levels of phagocytic capacity (number of C. albicans cells ingested per 100 macrophages). (B) Incubation with a corticosterone concentration of 0.72 mumol l-1 (similar to that observed in plasma immediately after exercise) raised the phagocytic capacity (144 +/- 12 after incubation with 0.72 mumol l-1 vs. 93 +/- 19 after incubation with 0.24 mumol l-1). This increase was also significantly greater than that observed with 7.2 mumol l-1 corticosterone. 4. It is concluded that corticosterone may mediate the increased phagocytic function of peritoneal macrophages induced by exercise.

Alterations in the immune response of golden hamsters during the course of Leishmania donovani infection and after treatment with sodium stibogluconate

The immune response of golden hamsters was monitored following experimental infection with Leishmania donovani and subsequent treatment with sodium stibogluconate (Stibanate Sb v) taking macrophage migration index (MMI), phagocytic activity of peritoneal macrophages, blastogenic response of splenocytes in presence of phytohaemagglutinin (PHA) and specific antibodies to Leishmania antigen, as parameters. MMI, a correlate of macrophage activation and cellular immune response (CMI) decreased to a value of 0.46 ± 0.09 (in infected hamsters) from the normal control value of 1.0 on day 21 post infection (p.i.). The value remained suppressed during the course of observation up to day 54 p.i. in untreated animals. Following stibanate treatment from day 21 p.i. the MMI started rising and was restored to slightly above the normal value (1.20 ± 0.12) on day 54 p.i. The phagocytic activity of peritoneal macrophages using 144c leucine labelled Escherichia coli and blastogenic response of splenocytes to PHA did not alter during the infection or after stibanate treatment. The specific humoral response to promastigote antigen as assessed by enzyme-linked immunosorbent assay (ELISA) revealed the appearance of antileishmanial antibodies on day 14 p.i., which gradually reached a peak titre of 1 :3200 on day 34 p.i. On stibanate treatment the antileishmanial antibodies started declining after day 7 post treatment (p.t.) and reached almost normal level on day 28 p.t. These observations strengthen the claim that hamsters can be used as a useful model for the study of the immune response in human visceral leishmaniasis.

Cytometric profile of molybdenum-induced contact sensitization versus a strong allergen reaction to oxazolone in murine auricular lymph node (ALN) test

Induction of contact hypersensitivity (CH) by molybdenum chloride (MoCl 5) was determined by auricular lymph node (ALN) test in C57B1/6 mice. The ALN test was further improved by immunophenotyping and cytometric analysis of subset-specific cells in the draining node. Skin sensitization was induced by topical ear exposure to 1.0–5.0% oxazolone and resulted in a strong dose-related ALN reaction. Analogous exposure to MoCl 5 resulted in a weaker but marked dose-related reaction, also manifested as an increase in cell number/ALN. Other differences between the oxazolone-induced strong sensitization and the MoCl 5-related ALN reaction were: (1) an increase in the total number of Ig + cells, which was, however, unchanged in the MoCl 5-exposed mice; (2) a significant increase in the total number of large/activated T-cell subsets; and (3) a marked shift in the relative percentage of gated large/activated subsets of ALN cells, which was not observed in the MoCl 5-exposed animals. Thus, it appeared that the molybdenum exposure induced a nonspecific increase in the cell number/ALN and was not accompanied by any marked activation of the T-cell subsets. Immunotoxicity of a 14 day subchronic exposure to MoCl 5 at 1–100 ppm in food was studied by quantification of splenic humoral IgM response to sheep erythrocytes (SRBC). Plaque-forming cells (PFC) and enzyme-linked immunosorbent assay (ELISA) revealed unchanged humoral exposure in MoCl 5-exposed mice. Cytometric assay of fluorescent beads uptake showed unchanged phagocytic activity of peritoneal macrophages from the MoCl 5-exposed mice. Immunophenotyping of CD4 +, CD8 +, Thy 1.2 + and Ig + cells revealed no effect of MoCl 5 exposure on the total count of cell subsets in the ungated populations of spleen, lymph nodes and peripheral blood cells. Molybdenum chloride should thus be considered as a non-immunotoxic and a weak, nonspecific contact irritant.

Oocyst production and immunogenicity of Cryptosporidium baileyi in chickens and mallards.

Two-day-old chickens and mallards were orally inoculated with one of 5 doses varying from 2 x 10(2) to 2 x 10(6) of C. baileyi oocysts per individual. Generally, the more oocysts inoculated were, the longer the patent periods were, and the more oocysts shedding were. Meanwhile increasing the inoculative dose, the prepatent periods were shortened except that mallards inoculated with 2 x 10(2) and 2 x 10(3) oocysts failed to produce the oocysts. The more parasites involving oocysts appeared from the chicken in comparison to the mallard. In the chickens challenged with a single dose of 2 x 10(6) oocysts, a small number of oocysts were detected from feces on days 4-14 after challenge infection (ACI) in all of carrageenan administered groups and in the control groups inoculated with 2 x 10(2) and 2 x 10(3) oocysts. In the mallards, a few oocysts were also recognized on days 5-15 ACI in all of carrageenan treated groups and in the control groups inoculated with 2 x 10(2), 2 x 10(3) and 2 x 10(4) oocysts. Just prior to challenge infection, phagocytic activity of peritoneal macrophages (Mø) and the number of peripheral Mø in both birds were significantly decreased in the carrageenan treated groups as compared to the control groups. Mild challenge infection in both birds denoted that the immunogenicity of C. baileyi to the birds was very strong, despite Mø blocker carrageenan administration.

Oocyst production and immunogenicity of Cryptosporidium muris (strain MCR) in mice.

Three-week-old ICR SPF mice were orally inoculated with one of 5 doses ranging from 2 x 10(2) to 2 x 10(6) oocysts of Cryptosporidium muris (strain MCR) per mouse. Oocyst inoculation was directly proportional to the amount of oocysts shed and was inversely proportional to the period required for peak oocyst production and to the prepatent period. Peak oocyst production occurred between fifteen and thirty-one days with a patent period from 61 to 64 days. Three days after all mice stopped shedding oocysts, they were orally challenged with a single dose of 2 x 10(6) oocysts of the same species. Marked seroconversion for IgG antibody accompanied recovery from mice inoculated with 5 x 10(5) oocysts. Mice administered with carrageenan excreted a small number of oocysts for 49.0 days on the average after challenge inoculation (ACI) and control mice for 14.2 days in a dose-independent fashion. Just before challenge infection, phagocytic activity of peritoneal macrophages (M phi) and the number of peripheral M phi were dramatically decreased. Mild challenge infection implies that the immunogenicity of C. muris (strain MCR) is very strong, despite M phi blocker carrageenan administration.

Enhancement of in vitro nonspecific immune functions by African plant extracts

AbstractThe in vitro immunomodulatory activities of extracts from African medicinal plants have been studied. Certain extracts exerted enhancing effects in a concentration dependent manner on immune cells from three different strains of mice. Among these were an enhancement of phagocytic activity of peritoneal macrophages and tumoricidal potential of macrophages, and stimulation of the oxidative burst of macrophages and granulocytes. In contrast, the proliferative capacity of lymphocytes was only marginally affected. Enhanced macrophage and granulocyte activation was also detected using leucocytes of the LPS nonresponder strain C3H/HeJ. From the latter it can be concluded that the observed stimulatory effects of the plant extracts in vitro were not due to contamination with lipopolysaccharides.

Stimulation of peritoneal macrophage activity in rats with experimental peritonitis during transfusion of UV-irradiated blood

Three transfusions of blood irradiated at 254 nm induce an increase of phagocytic activity of peritoneal macrophages in rats with peritonitis in comparison with infusion of intact blood. Addition of aspirin, an inhibitor of enzymatic peroxidation of lipids, to the irradiated portion of the blood before irradiation abolishes this stimulating effect.

Effect of Vitamin E Supplementation on the Immune Response during Chemically Induced Hepatocarcinogenesis in the Rat.

The effect of vitamin E (Vit E), both α-tocopherol (α-T) and γ-tocotrienol (γ-T3), supplementation on splenocyte proliferation and phagocytic activity of peritoneal macrophages in rats treated with diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) was investigated. Splenocyte proliferation in response to concanavalin A or phytohemagglutinin and phagocytic activity of peritoneal macrophages in the DEN/AAF-treated rats were significantly reduced compared with the control levels. In contrast, mitogenesis and phagocytic activity of peritoneal macrophages were increased significantly in the DEN/AAF-treated rats supplemented with Vit E; and the vitamin effect was dose dependent. However, the increases were not so great as those observed in the controls. The highest doses of α-T and γ-T3 used effected the highest phagocytic activity, with α-T generally showing a higher activity than γ-T3. Although long-term Vit E supplementation at half the optimum dose significantly increased mitogenesis, phagocytic activity in the DEN/AAF-treated and control rats was only marginally increased.

Immunomodulation by morphine in [formula omitted][formula omitted]-infected mice

The effect of morphine on immunomodulation and host defense have been investigated during Plasmodiumbergheiinfection in BALB/c mice. A single low (5.0 mg/kg) subcutaneous dose of morphine strongly suppressed (sometimes completely eliminated) the parasitaemia, whereas a high dose (80.0 mg/kg) exerted mild potentiating effect. Mice treated with the low dose showed a significant (p < 0.05) increase in the total number of circulating leukocytes, the number (pool-size) of peritoneal macrophages, and the phagocytic activity of peritoneal macrophages, invitro. Conversely, in mice treated with the high dose, all these parameters were diminished. Silica (3.0 mg/mouse), administered intravenously, abrogated the morphine-induced protective effects but did not affect its potentiation of the infection. Naloxone pretreatment (4.0 mg/kg) completely blocked the protective effects of morphine, suggesting the mediation via naloxone-sensitive opiate-receptors; paradoxically, it did not affect the potentiating effects. These observations indicate that morphine exerted a dose-dependent, biphasic effect on the course of P.bergheiinfection in mice, apparently by modulating the macrophage-mediated protective mechanisms.