Binding of ssDNA-antibody complexes to thioglycollate-induced mouse peritoneal macrophages in the presence of serum

The binding of DNA-antibody complexes to thioglycollate-induced mouse peritoneal macrophages is inhibited by fresh but not by decomplemented normal mouse serum. Binding to macrophage complement receptors was not observed.     

Stimulation of the phagocytic function in guinea pig peritoneal macrophages by physical activity stress

Summary A study was made of all the different stages of the phagocytic function in peritoneal macrophages from male guinea pigs [3 (SD 1) months old] before, immediately after, and 24 h after being subjected to stress from physical activity (swimming until exhaustion). The early (10 min) and late (40 min) adherence to tissue substrates, chemotaxis, attachment and phagocytosis ofCandida albicans, ingestion of inert particles (latex beads), and basal oxidative metabolism [measured by nitroblue tetrazolium (NBT) reduction] were significantly stimulated by the physical activity. After 24 h, late adherence, attachment capacities, and basal oxidative metabolism returned to basal values, whereas early adherence, chemotaxis, phagocytosis of cells and inert particles, and microbicidal capacity (production of superoxide anion measured by NBT reduction in presence of ingested material) remained significantly increased. The stress produced by physical activity, reflected in increased serum corticosterone values, led to a global stimulation of the phagocytic function.     

Small alveolar macrophages are infected preferentially by HIV and exhibit impaired phagocytic function

HIV-1-infected persons are at higher risk of lower respiratory tract infections than HIV-1-uninfected individuals. This suggests strongly that HIV-infected persons have specific impairment of pulmonary immune responses, but current understanding of how HIV alters pulmonary immunity is incomplete. Alveolar macrophages (AMs), comprising small and large macrophages, are major effectors of innate immunity in the lung. We postulated that HIV-1 impairs pulmonary innate immunity through impairment of AM physiological functions. AMs were obtained by bronchoalveolar lavage from healthy, asymptomatic, antiretroviral therapy-naive HIV-1-infected and HIV-1-uninfected adults. We used novel assays to detect in vivo HIV-infected AMs and to assess AM functions based on the HIV infection status of individual cells. We show that HIV has differential effects on key AM physiological functions, whereby small AMs are infected preferentially by the virus, resulting in selective impairment of phagocytic function. In contrast, HIV has a more generalized effect on AM proteolysis, which does not require direct viral infection. These findings provide new insights into how HIV alters pulmonary innate immunity and the phenotype of AMs that harbors the virus. They underscore the need to clear this HIV reservoir to improve pulmonary immunity and reduce the high incidence of lower respiratory tract infections in HIV-1-infected individuals.     

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. Translated fromByulleten Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 3, pp. 315—318, March, 1998     

Limits of phagocytic power of macrophages

The ability of peritoneal macrophages to take up different doses of antigen (sheep's erythrocytes) and of antigens differing in physicochemical properties (sheep's erythrocytes, rat erythrocytes, and typhoid vaccine) was studied. An increase in the dose of sheep's erythrocytes injected many times over had no effect on the quantity of antigen ingested by the macrophages within a definite time interval. In macrophages taken at short periods after injection of erythrocytes of the different species of animals into the mice, ability to take up these erythrocytes in vitro was sharply inhibited. Preincubation of macrophages (in vivo or in vitro) with all the antigens tested sharply increased their ability to phagocytose typhoid vaccine.Laboratory of Physiology and Regulation of Immunity, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. A. Vershilova.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsina, Vol. 84, No. 7, pp. 58–61, July, 1977.     

Changes of structure and function of spleen macrophages induced by malignant neoplasia

Spleen macrophages, as most active elements of the mononuclear phagocyte system, were studied using light and electron microscopy in experimental rats and mice with differenet types of malignant neoplasia, including chemically induced carcinogenesis, transplantable tumor growth and in leukosis. In chemically induced carcinogenesis macrophage phagocytic activity was reduced, morphologically, the cellular surface smoothing, cytoplasm organell reduction and nuclear pyknotic changes were found. In animals with transplanted tumors, high activity of spleen macrophages was detected. In animals with leukosis, macrophages are characterized by reduced phagocytic activity, smoothed cellular surface and a variable number of lysosomes. The results obtained support the concept of high reactivity of the cells of mononuclear phagocyte system in neoplasia.     

Plasticity of antimicrobial and phagocytic programs in human macrophages

Macrophage (MΦ) polarization is triggered during the innate immune response to defend against microbial pathogens, but can also contribute to disease pathogenesis. In a previous study, we found that interleukin-15 (IL-15) -derived classically activated macrophages (M1 MΦ) have enhanced antimicrobial activity, whereas IL-10-derived alternatively activated macrophages (M2 MΦ) were highly phagocytic but lacked antimicrobial activity. Given that the ability to modulate MΦ polarization from M2 MΦ to M1 MΦ may promote a more effective immune response to infection, we investigated the plasticity of these MΦ programs. Addition of IL-10 to M1 MΦ induced M2-like MΦ, but IL-15 had little effect on M2 MΦ. We determined the set of immune receptors that are present on M2 MΦ, elucidating two candidates for inducing plasticity of M2 MΦ, Toll-like receptor 1 (TLR1) and interferonγ (IFN-γ) receptor 1. Stimulation of M2 MΦ with TLR2/1 ligand (TLR2/1L) or IFN-γ alone was not sufficient to alter M2 MΦ phenotype or function. However, co-addition of TLR2/1L and IFN-γ re-educated M2 MΦ towards the M1 MΦ phenotype, with a decrease in the phagocytosis of lipids and mycobacteria, as well as recovery of the vitamin-D-dependent antimicrobial pathway compared with M2 MΦ maintained in polarizing conditions. Similarly, treatment of M2 MΦ with both TLR2/1L and anti-IL-10 neutralizing antibodies led to polarization to the M1-like MΦ phenotype and function. Together, our data demonstrate an approach to induce MΦ plasticity that provides the potential for re-educating MΦ function in human mycobacterial disease to promote host defense and limit pathogenesis.     

Changes in phagocytic function with glycaemic control in diabetic patients.

Phagocytic function was assessed by serial whole blood chemiluminescence in poorly controlled type 2 (non-insulin dependent) diabetic patients during efforts to improve glycaemic control and compared with a group of well controlled type 1 (insulin dependent) diabetic patients. Chemiluminescence (corrected to a standard polymorphonuclear count) remained below normal (0.15-0.30 photons/second/cell) for most of the type 2 patients until 12 weeks when the value was significantly increased in patients showing improved glycaemic control (mean (range) 0.25 (0.01-0.43) photons/second/cell) compared with those showing no improvement (0.12(0.01-0.31) photons/second/cell). There was a significant inverse correlation of delta HbA1 with delta chemiluminescence. Although mean chemiluminescence for the type 1 diabetic patients was within the normal range, there was a wide scatter of values (0.19 (0.04-0.43) photons/second/cell) and there was no significant difference compared with the final value of type 2 patients with improved control. Glycaemic control is therefore a major determinant of phagocytic function in diabetic patients, but other factors must contribute, particularly in type 1 (insulin dependent) patients.     

Modulation of phagocytic function in murine peritoneal macrophages by bombesin, gastrin-releasing peptide and neuromedin C.

Bombesin, as well as the two mammalian bombesin-like peptides gastrin-releasing peptide and neuromedin C, have been shown in this study to stimulate in vitro all steps of the phagocytic process in murine peritoneal macrophages: adherence to substrate, chemotaxis, ingestion of cells (Candida albicans) and inert particles (latex beads), and production of superoxide anion as measured by nitroblue tetrazolium reduction. A dose-response relationship was observed, with maximal stimulation of phagocytic process between 10(-12)M and 10(-9)M. Gastrin-releasing peptide (GRP) and neuromedin C caused a higher activation of adherence, chemotaxis and ingestion of C. albicans than bombesin. The three neuropeptides induced in murine macrophages a significant, but transient, increase of inositol 1,4,5-trisphosphate (IP3) levels at 60 seconds. On the contrary, these neuropeptides produced a rapid, transient and significant decrease of cAMP at 30 seconds. These results suggest that there are close relations between IP3 and cAMP messenger systems and the phagocytic process in murine peritoneal macrophages when these cells are incubated in the presence of bombesin, GRP or neuromedin C.     

Hypothermia affects the phagocytic activity of rat peritoneal macrophages

To examine the effect of hypothermia on the phagocytic capacity of rat peritoneal macrophages for latex particles, male Wistar rats were exposed to 4 degrees C for 8 and 72 h. While the shorter exposure to cold did not affect body temperature and macrophage function, animals exposed to 4 degrees C for 72 h showed a mean decrease of their body temperature by 1.5 degrees C. The superoxide anion production was significantly increased whereas the number of phagocytic cells decreased. In addition, the mean number of latex particles engulfed by each individual cell was lower than that of controls. Peripheral blood mononuclear cells (PBMC) of these animals showed lower mitogen response to phytohaemagglutinin (PHA), while that for concanavalin A (Con-A) remained unchanged. Peritoneal macrophages exposed in vitro to 24 degrees C for 60 min showed a decreased phagocytic capacity in comparison with macrophages kept at 37 degrees C, an observation suggesting the development of an indigenous cell defect for phagocytosis at lower temperatures. On the other hand, the effect of additional humoral factor(s) on macrophage activity, such as an increase in serum level of catecholamines and corticosterone, cannot be excluded. The results of the study may contribute to understanding the predisposition to infections during exposure to cold.     

Persistent accumulation of gut macrophages with impaired phagocytic function correlates with SIV disease progression in macaques

The contribution of macrophages in the gastrointestinal tract to disease control or progression in HIV infection remains unclear. To address this question, we analyzed CD163⁺ macrophages in ileum and mesenteric lymph nodes (LN) from SIV‐infected rhesus macaques with dichotomous expression of controlling MHC class I alleles predicted to be SIV controllers or progressors. Infection induced accumulation of macrophages into gut mucosa in the acute phase that persisted in progressors but was resolved in controllers. In contrast, macrophage recruitment to mesenteric LNs occurred only transiently in acute infection irrespective of disease outcome. Persistent gut macrophage accumulation was associated with CD163 expression on α4β7⁺CD16⁺ blood monocytes and correlated with epithelial damage. Macrophages isolated from intestine of progressors had reduced phagocytic function relative to controllers and uninfected macaques, and the proportion of phagocytic macrophages negatively correlated with mucosal epithelial breach, lamina propria Escherichia coli density, and plasma virus burden. Macrophages in intestine produced low levels of cytokines regardless of disease course, while mesenteric LN macrophages from progressors became increasingly responsive as infection advanced. These data indicate that noninflammatory CD163⁺ macrophages accumulate in gut mucosa in progressive SIV infection in response to intestinal damage but fail to adequately phagocytose debris, potentially perpetuating their recruitment.     

Rainbow trout macrophages in vitro: Morphology and phagocytic activity

The properties of macrophages from the pronephros of Rainbow trout (Salmo gairdneri Richardson) were studied in vitro. We found that phagocytes obtained from the pronephros constitute a non-homogeneous cell population. Three populations with different adherence properties were examined with special emphasis on morphology and phagocytic capacity. The differentiation of the three populations in culture was similar morphologically, and their phagocytic activity showed only small variations. The methods for cell separation and culture reported here are a useful tool for gaining better understanding of how Rainbow trout macrophages function in the immune response.     

Involvement of the spleen in murine B cell differentiation

Experiments were performed to study the influence of neonatal and adult splenectomy on B cell differentiation in mice. Lymph node cells of both groups were found to contain a significantly higher proportion of Ig-bearing cells. Moreover, these cells expressed a higher density of membrane Ig and a higher IgM/IgD ratio. In addition, the response of these cells to different polyclonal B cell activators, especially dextran sulfate, was much higher than the response of the sham-operated controls. Similar experiments were carried out in splenectomized and control animals that were lethally irradiated and reconstituted with different hemopoietic cell sources. The same pattern of results was obtained, except when reconstituting the irradiated animals with fetal liver cells. These experiments, which were performed at long time intervals post splenectomy, show that in the absence of the spleen, there is an accumulation of less mature B cells in the periphery implying an active role of the spleen in at least certain differentiation steps of the B cell lineage.     

Effect of blastolysin on the ultrastructure and phagocytic activity of peritoneal macrophages

Morphology and functional activity of peritoneal macrophages were studied at different intervals after the administration of blastolysin to Wistar rats. Alteration of the macrophage ultrastructure and their functional activity proving the stimulatory effect of the preparation on cells is shown. The signs of stimulation were revealed 30 minutes after the administration of the drug, reached a maximum on the 7th and 14th days and was manifested by structural changes of the cell surface, lysosomal apparatus, mitochondria and by activation of phagocytosis.     

Candida albicans metabolite affects the cytoskeleton and phagocytic activity of murine macrophages

Candida albicans is the most common opportunistic fungal pathogen of humans, causing systemic disease in immunocompromised patients. Host resistance to C. albicans infections is mediated predominantly by neutrophils and monocytes/macrophages. We have previously shown that exposure of a human epithelial cell line (HEp2) to C. albicans or to a culture filtrate of C. albicans caused actin rearrangement in the HEp2 cells. Since shifting of actin from the filamentous to the globular form may be crucial to the activity of phagocytes, we assessed in the present study the effect of the C. albicans metabolite (lyophilized culture filtrate) on the cytoskeleton of murine peritoneal macrophages and on their phagocytic activity. Our results showed a significant decrease in phagocytosis of C. albicans, ranging from 53-63% and a 25% reduction for C. glabrata cells. Using confocal laser scanning microscopy an actin rearrangement in the macrophages could be demonstrated that may be associated with the decrease of phagocytosis. We also tested the effect of mannan and of the secreted aspartic proteinase (Sap) inhibitor--pepstatin, on the activity of the metabolite in order to define the putative component and found no influence. In conclusion, our data indicate that a C. albicans metabolite affects phagocytic activity of macrophages, probably by alterations in their cytoskeleton.     

Effect of leukocytic pyrogen on the phagocytic properties of macrophages in tissue culture

The effect of rabbit leukocytic pyrogen (LP) on the phagocytic activity of peritoneal macrophages from albino mice toward shigellas was investigated. The effect was found to depend on dose: LP in a large dose inhibited phagocytosis whereas small doses of LP were not very effective; the addition of LP to macrophages in average doses, after administration of kanamycin, stimulated both the phase of ingestion and the phase of digestion of the shigellas. Stimulation of phagocytosis by LP was accompanied by an increase in the activity of the lysosomal enzyme acid phosphatase in the macrophages; changes in the RNA content were not significant.Department of General Pathology, Institute of Experimental Medicine, Leningrad. Department of Infectious Diseases, I. P. Pavlov First Leningrad Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 12, pp. 700–703, December, 1978.