Phagocytic Potential Of Macrophages Research Articles

Pathological effects of feeding aflatoxin-contaminated feed on immune status and reproductive performance of juvenile white leghorn males and its mitigation with ∝-tocopherol and Moringa oleifera.

This study was planned to detect the adverse pathological consequences of aflatoxin B1 in White Leghorn (WLH) layer breeder males. Eight-week-old male layer cockerels were separated into six experimental categories: A group was kept as negative control, offered with normal feed only; group B was fed with 400ppb amount of aflatoxin, while groups F and D fed with normal feed and supplemented with vitamin E 100ppm and 1% Moringa oleifera, respectively, whereas groups E and C were fed with 400ppb aflatoxin containing feed and ameliorated with vitamin E 100ppm and 1% Moringa oleifera, respectively. This study was continued for 2months and immunologic disorders and reproductive parameters were observed during the trial. To find out immunological status lymphoproliferative response to phytohemagglutinin-P (PHA-P), antibody titers against sheep red blood cells (SRBCs) and carbon clear assay were performed by collecting samples from five birds from each group. The whole data was measured by ANOVA test, and group means were compared by DMR test by using M-Stat C software. Regarding the reproductive status, spermatogenesis, blood testosterone level, testes weight, testes histology, sperm motility, and morphology were negatively affected by aflatoxins, but these deviations positively ameliorated by vitamin E and Moringa. Vitamin E and Moringa found advantageous in boosting the immune status of affected bird.All the immunological parameters including antibody titers against sheed red blood cells, lymphoproliferativeresponse to avian tuberculin and phagocytic potential of macrophages were suppressed by AFB1 however incontrol, Moringa and vitamin E groups these immunological responses were significantly higher.

Spatial confinement downsizes the inflammatory response of macrophages.

Macrophages respond to chemical/metabolic and physical stimuli, but their effects cannot be readily decoupled in vivo during pro-inflammatory activation. Here, we show that preventing macrophage spreading by spatial confinement, as imposed by micropatterning, microporous substrates or cell crowding, suppresses late lipopolysaccharide (LPS)-activated transcriptional programs (biomarkers IL-6, CXCL9, IL-1β, and iNOS) by mechanomodulating chromatin compaction and epigenetic alterations (HDAC3 levels and H3K36-dimethylation). Mechanistically, confinement reduces actin polymerization, thereby lowers the LPS-stimulated nuclear translocation of MRTF-A. This lowers the activity of the MRTF-A-SRF complex and subsequently downregulates the inflammatory response, as confirmed by chromatin immunoprecipitation coupled with quantitative PCR and RNA sequencing analysis. Confinement thus downregulates pro-inflammatory cytokine secretion and, well before any activation processes, the phagocytic potential of macrophages. Contrarily, early events, including activation of the LPS receptor TLR4, and downstream NF-κB and IRF3 signalling and hence the expression of early LPS-responsive genes were marginally affected by confinement. These findings have broad implications in the context of mechanobiology, inflammation and immunology, as well as in tissue engineering and regenerative medicine.

Investigations into the Immunostimulatory Activities of the Compounds Isolated from Zizyphus mauritiana

Objective: Any lacuna in the immune system can cause serious problems. Many synthetic immunostimulators are available, but they show many side effects. Phytochemicals present in Zizyphus mauritiana, Lam (Rhamnaceae) can act as natural immunostimulators. In the present study, natural and potent immunostimulatory compounds were isolated from Zizyphus mauritiana and their immunostimulatory activities were studied. Methods: Extracts of the stem bark were prepared in various solvents in the increasing order of polarity. These extracts were tested for their potential to stimulate phagocytosis. Ethanolic extract of stem bark, which was found to be effective in stimulating phagocytosis in macrophages, was further purified by adsorption column chromatography to get effective fraction termed as effective immunostimulatory fraction (EIF). EIF was tested for its potential to stimulate phagocytosis in macrophages, to induce proliferation in lymphocytes as well as splenocytes and to stimulate antibody formation in Wistar rats. Results: Phytochemical analysis of EIF indicated that it is rich in alkaloids. On treatment with EIF (1 μg/ml), phagocytic potential of macrophages was raised 6 times, while on EIF treatment (100 μg/ml) lysosomal enzyme activity was doubled. Splenocytes and lymphocytes were found to proliferate with a stimulation index of 5 and 6 respectively, on treatment with EIF (10 μg/ml). In vivo, EIF was found to trigger antibody formation two times, elevate leucocyte count (by 700/Cu mm) and increase the weight of thymus (3 times) as well as spleen (1.3 times) as compared to control on oral administration to Wistar rats (10 mg/kg body weight). Conclusions: Results of the experiments revealed that phytochemicals present in EIF appear to be excellent immunostimulators and can act as replacement for synthetic immunostimulators.

Lack of galectin‐3 speeds Wallerian degeneration by altering TLR and pro‐inflammatory cytokine expressions in injured sciatic nerve

Wallerian degeneration (WD) comprises a series of events that includes activation of non-neuronal cells and recruitment of immune cells, creating an inflammatory milieu that leads to extensive nerve fragmentation and subsequent clearance of the myelin debris, both of which are necessary prerequisites for effective nerve regeneration. Previously, we documented accelerated axon regeneration in animals lacking galectin-3 (Gal-3), a molecule associated with myelin clearance. To clarify the mechanisms underlying this enhanced regeneration, we focus here on the early steps of WD following sciatic nerve crush in Gal-3(-/-) mice. Using an in vivo model of nerve degeneration, we observed that removal of myelin debris is more efficient in Gal-3(-/-) than in wild-type (WT) mice; we next used an in vitro phagocytosis assay to document that the phagocytic potential of macrophages and Schwann cells was enhanced in the Gal-3(-/-) mice. Moreover, both RNA and protein levels for the pro-inflammatory cytokines IL-1β and TNF-α, as well as for Toll-like receptor (TLR)-2 and -4, show robust increases in injured nerves from Gal-3(-/-) mice compared to those from WT mice. Collectively, these data indicate that the lack of Gal-3 results in an augmented inflammatory profile that involves the TLR-cytokine pathway, and increases the phagocytic capacity of Schwann cells and macrophages, which ultimately contributes to speeding the course of WD.

In vivo and ex vivo phagocytic potential of macrophages from progeny of breeder hens kept on ochratoxin A (OTA)-contaminated diet

This study aimed to investigate the phagocytic potential of macrophages in progeny of breeder hens kept on an OTA-contaminated diet. For this purpose, 84 White Leghorn (WL) layer breeder hens (40-weeks-of-age) were divided into seven groups (A–G). Hens in Group A were fed a commercial layer ration while those in Groups B–G were kept on a diet amended with 0.1, 0.5, 1.0, 3.0, 5.0, or 10.0 mg OTA/kg, respectively, for up to 3 weeks (n = 12/treatment group; n = 4/time sub-group/treatment group). Fertile eggs were set for hatching on a weekly basis to get the progeny of each week separately. Hatched chicks (n = 10 from each group) were injected with India ink at day 14-of-age to study the in vivo phagocytosis of carbon particles. At day 30, abdominal macrophages were collected from 15 chicks/group and were used to assess their ex vivo/in vitro phagocytic potential against sheep red blood cells (SRBC) as well as for nitrite production upon challenge with lipopolysaccharide (LPS). The phagocytic indices of the reticuloendothelial system of all three sets of progeny (chicks obtained from hens fed OTA for 7, 14, and 21 days) were significantly lower than values seen with Group A chicks. The number of macrophages that were actively phagocytic, the number of SRBC internalized per macrophage, and the extent of nitrite production after stimulation with LPS were each significantly lower in the cells obtained from chicks of breeder hens that had been maintained on the OTA-contaminated diets. The findings of this study clearly showed that there are immunosuppressive effects—in terms of depressed in vivo and in vitro macrophage functionality—in progeny of OTA-fed breeder hens.

Effect of vitamin D3 on phagocytic potential of macrophages with live Mycobacterium tuberculosis and lymphoproliferative response in pulmonary tuberculosis.

Immune responses are elicited through antigen presentation and recognition by macrophages and T-lymphocytes, respectively. The immunomodulatory effect of vitamin D(3) on macrophage phagocytic potential with live Mycobacterium tuberculosis, spontaneous and M. tuberculosis culture filtrate antigen induced lymphocyte responses were studied in pulmonary tuberculosis patients (PTBPs) ( n = 31) and normal healthy subjects (NHSs) ( n = 43). Vitamin D(3) at a concentration of 10(-7) M significantly enhanced the macrophage phagocytosis of live M. tuberculosis in normal subjects with low phagocytic potential (less than 10%) ( p = 0.015). No such increase was observed in PTBPs. Vitamin D(3) significantly decreased the spontaneous lymphoproliferative response ( p = 0.022) and increased the apoptosis of peripheral blood mononuclear cells in PTBPs ( p = 0.024). In normals, vitamin D(3) increased the spontaneous lymphoproliferative response. An inverse correlation between macrophage phagocytosis and spontaneous response was observed in NHSs, whereas a direct correlation was seen between vitamin D(3)-treated cells in normal subjects under in vitro condition. Vitamin D(3) decreased the M. tuberculosis culture filtrate antigen induced lymphocyte response significantly in normal subjects ( p = 0.0003), while it had no influence on the lymphocyte response in PTBPs. The present study suggests that exposure to vitamin D(3) increases the phagocytic potential and spontaneous lymphoproliferative response but brings down the antigen-induced response in normals. In tuberculosis, addition of vitamin D(3) has no significant effect on antigen-induced lymphoproliferative response. This may be due to the unresponsive nature of the cells to the action of vitamin D(3) by virtue of the disease, which renders them inactive.

A Comparative Analysis of Immunorestoration and Recovery with Conventional and Immunotherapeutic Protocols in Canine Generalized Demodicosis: A Newer Insight of Immunotherapeutic Efficacy of T11TS

Demodex canis is a natural inhabiting mite of canine skin. Immunological disorder or genetic disorder induces the Demodex population to proliferate vigorously resulting in generalized demodicosis with consequent chronic immunosuppression. Signs of generalized demodicosis include alopecia, crysting, erythema, secondary pyoderma etc. Amitraz, an acaricide, is used conventionally for the treatment of generalized demodicosis. In many instances, the disease relapses due to the residual immunosuppression. The need of an immunorestorative therapy has been urged in generalized demodicosis. Two immunorestorative drugs, namely, Immuplus, a herbal drug, and T11TS, a sheep erythrocyte surface glycoprotein, has been used in two separate groups of dogs having generalized demodicosis and receiving Amitraz treatment. It was observed that though Amitraz treated group responded to the therapy showing increased E‐rosettes and nonspecific cytotoxic efficacy of T‐lymphocytes and decrease in phagocytic potential of macrophages, the groups treated with the immunotherapeutics like Immuplus and T11TS, responded better. However, the group treated with T11TS showed best recovery. These results emphasize the need for an immunorestorative therapy in generalized demodicosis and provide data in favor of T11TS as a better immunomodulator in comparison to Immuplus.

Modulation of Biochemical and Cytological Profile of Bronchoalveolar Lavage Constituents in Rats Following Split-Dose Multiple Inhalation Exposure to Methyl Isocyanate

1. Studies were carried out to explore the acute pulmonary effects of equal, split-dose, multiple inhalation exposures of rats to methyl isocyanate (MIC), (0.32 mg l-1, 8 min x 10 exposures) as reflected by alterations in bronchoalveolar lavage fluid (BALF) constituents and to evaluate recovery, if any, following survival in a MIC-free environment, 10 d after the last MIC exposure. 2. In the BALF of MIC-exposed rats, there was an increase in the total number of cells and the number of cells showing enhanced dye uptake and reduction of nitroblue tetrazolium chloride. The cell-free BALF showed increases in total protein, sialic acids and lactic acid contents and lactate dehydrogenase activity. 3. In rats exposed to MIC and sacrificed 10 d after survival in a MIC-free environment, there was a reduction in the cellular and biochemical constituents of BALF. The phagocytic potential of macrophages was, however, also decreased under this regime.

Phagocytic potential of macrophages from within delayed hypersensitivity-mediated granulomata.

The phagocytic potential of macrophages from within granulomas associated with delayed hypersensitivity was studied in guinea-pigs sensitised with FCA and challenged either with PPD or live M. tuberculosis. The results show that FCA treatment induces a 30 percent increase in phagocytosis of IgG coated erythrocytes by macrophages which migrate into a foreign body granuloma. PPD treatment enhances this index to about 70 per cent. When live M. tuberculosis was used as antigen the phagocytic index of macrophages from lesions induced in sensitised animals was about 50 per cent. higher than in controls. The increase in phagocytosis by macrophages was maximal at 4 days and decreased 8 and 16 days after challenge, in both sensitised and non-sensitised animals. The results show that in granulomas associated with delayed hypersensitivity, macrophages have a transitory increase in their phagocytic activity. Later the older cells in the centre of the granuloma lose this property, thereby facilitating antigen persistence and chronicity.