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The clinical and pharmacological activities of ginseng are known to modulate immune function, metabolic processes and neuro-endocrine system activities. Ginseng saponins are the principle active ingredients in the formation of immune stimulating complexes. The objective of this study was to evaluate the in vitro effect of ginseng total saponin (GTS) on the phagocytic capacity of canine peripheral blood phagocytes. GTS itself did not cause any direct effect on the phagocytic capacity of peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) but not peripheral blood monocytes. However, the phagocytic capacity of PMN and monocytes, but not PBMC, was enhanced by the culture supernatant from PBMC treated with GTS. The phagocytic capacity of PMN and monocytes was also increased by treatment with recombinant canine (rc) tumor necrosis factor (TNF)-α. The ability of the culture supernatant from GTS-treated PBMC to stimulate the phagocytic capacity of phagocytes was inhibited by addition of anti-rc TNF-α polyclonal antibody (pAb) prior to the culture. The amount of TNF-α in the culture supernatant from PBMC was shown to increase upon treatment of GTS as compared with that of vehicle-treated PBMC culture supernatant. These results suggest that GTS has an immunoenhancing effect on the phagocytic capacity of canine peripheral blood phagocytes, which is mainly mediated by TNF-α released from GTS-stimulated PBMC.

Baicalin is the main active ingredient primary isolated from the Chinese herb, Scutellaria baicalensis Georgi. Although baicalin can induce M2 macrophage polarization, we still do not know the subtype of macrophages polarized by baicalin. In this study, we characterized that murine bone marrow derived macrophages induced by M-CSF can be further polarized into M2_C phenotype by baicalin. The signatures of M2_C macrophages for mRNA expression like interferon regulatory factor 4 (IRF4), interleukin-10 (IL-10), MERTK and PTX3 were up-regulated. Moreover, we observed the concomitantly decreasing of tumor necrosis factor alpha (TNF-$\alpha$), interferon regulatory factor 5 (IRF5), IL-6. In contrast, M2 macrophages polarized by IL-4 increased gene transcript of arginase-1 (Arg-1) and surface marker of CD206 indicates that their identity as M2_A rather than M2_C subtypes. Interestingly, the phagocytosis as well as efferocytosis activity were significantly enhanced in M2_C macrophage polarized by baicalin and these capacities were associated with the expression of MERTK receptor. Finally, we conclude that baicalin induced M2_C macrophages polarization with both elevations of efferocytosis and anti-inflammatory activity.

A mathematical model for the drug delivery to macrophages of the tissues by using a preassigned cohort of red blood cells loaded with a drug is presented. This model is a system of three nonlinear differential equations, with a discrete time delay and an input depending on the time. The input should be controlled in order to obtain the longest duration of the therapeutic effect.

In industrial swine production, several important viral diseases are frequently complicated with bacterial infections, suggestive of virus–bacteria synergism. Although most virus-induced leukocyte dysfunctions are attributed to monocytes and lymphocytes, the role of polymorphonuclear cells (PMNs, mainly neutrophils) should not be excluded, because they are the first leukocytes to respond to inflammation. Previous studies indicated that pseudorabies virus (PrV) blocked the indirect recruitment of PMNs by inhibiting the production of interleukin-8 by primed peripheral blood mononuclear cells (PBMCs) and also reduced the phorbol 12-myristate 13-diacetate (PMA)-induced oxidative burst (OB) in PMNs. This study used PrV as a model to explore other possibilities of virus-induced PMN dysfunctions in pigs. The goals were: (1) to develop assay for simultaneous evaluation of phagocytosis and OB to Actinobacillus pleuropneumoniae (APP) and (2) to evaluate whether PrV could affect these responses to APP in an ex vivo setting. Approximately 12% of the PMNs underwent phagocytosis, as indicated by the presence of intracellular propidium iodide(PI)-labeled APP (PI-APP), and 32% of the PMNs launched OB to APP, as detected by dihydrorhodamine (DHR). Approximately 86% of those OB responsive cells did not contain engulfed PI-APP, and the OB was presumably induced by the bacteria lipopolysaccharide (LPS). Only 5 ± 1% of the cells underwent simultaneous phagocytosis and OB. Under certain conditions, PrV reduced the non-phagocytosis-associated OB by approximately 40% (p < 0.05), while the phagocytosis was unaffected overall. These results suggest that PrV may interfere with bacteria LPS-mediated signaling, suggesting a possibility of PrV-APP synergism in causing pneumonia.

Microglial activation plays an important role in neurodegenerative diseases. Once activated, they have macrophage-like capabilities, which can be beneficial by phagocytosis and harmful by secretion of neurotoxins. However, the resident microglia always fail to trigger an effective phagocytic response to clear dead cells or Aβ deposits during the progression of neurodegeneration. Therefore, the regulation of microglial phagocytosis is considered a useful strategy in searching for neuroprotective treatments. In this study, our results showed that low-power laser irradiation (LPLI) (20 J/cm²) could enhance microglial phagocytic function in LPS-activated microglia. We found that LPLI-mediated microglial phagocytosis is a Rac-1-dependent actin-based process, that a constitutively activated form of Rac1 (Rac1Q61L) induced a higher level of actin polymerization than cells transfected with wild-type Rac1, whereas a dominant negative form of Rac1 (Rac1T17N) markedly suppressed actin polymerization. In addition, the involvement of Rac1 activation after LPLI treatment was also observed by using a Raichu fluorescence resonance energy transfer (FRET)-based biosensor. We also found that PI3K/Akt pathway was required in the LPLI-induced Rac1 activation. Our research may provide a feasible therapeutic approach to control the progression of neurodegenerative diseases.

Ultrahigh molecular weight polyethylene (UHMWPE) wear particles-induced osteolysis and aseptic loosening is the main reason causing the failure of the total joint replacement. It is believed that cytokines, such as tumor necrosis factor-α (TNF-α), released by macrophages that are stimulated by UHMWPE particles can activate osteoclasts and facilitate osteolysis. In one of our previous studies, we have attempted to explain the effects of wear particles on bioactivity by analyzing the phagocytosis of particles from a biophysical viewpoint. By integrating the membrane surface areas of macrophages, we were able to estimate the maximum number of internalized particles, which is defined as the phagocytic capacity for a particle population. It has been found that for the particles with same total volume, the elongated particles have a smaller phagocytic capacity in comparison to the spherical particles. By further analyzing the cell culture and results of animal tests as reported in the literature, we found that the ratio of the particle concentration (no. of particles/no. of cells) to the phagocytic capacity is a critical value for the particles-induced biological responses. When this ratio is smaller than unity, the bioactivity is approximately proportional to the ratio itself; but limited change of biological response was observed when this ratio is larger than unity. In this study, we obtained further experimental evidence in support of this hypothesis. The proliferation and TNF-α release of macrophages when co-cultured with different dosages of UHMWPE particles in an inverted in vitro cell culture model were measured.