Enhancement of peritoneal macrophage activity by bovine gamma globulin in mice

Mice treated with bovine gamma globulins showed an increased resistance to Salmonella typhimurium infection. This phenomenon seems to be bound to an increase of peritoneal macrophage phagocytic activity, as shown by the method of chemiluminescence, in experiments performed on peritoneal macrophages from mice treated with bovine gamma globulin.     

Macrophages and neutrophils cooperate in immune responses to <Emphasis Type="Italic">Leishmania</Emphasis> infection

Neutrophils and macrophages are phagocytic cells that cooperate during inflammation and tissue repair. Neutrophils undergo apoptosis and are engulfed by macrophages. Engulfment modulates macrophage activation and microbicidal activity. Infection by Leishmania takes place in the context of tissue repair. This article discusses cellular and molecular mechanisms involved in the intimate cooperation of neutrophils and macrophages in Leishmania infection.     

Light dependent accumulation of macrophages at the photoreceptor-pigment epithelial interface in the retina of albino mice

Summary In the subretinal space of albino mice, macrophages appear from the time of eye opening and increase in number for 6 months; thereafter they decline with age. Dark rearing retards the accumulation of these cells, and exposure to constant light results in a rapid increase. Observations suggest that macrophages appear as a response to visual cell decay in albino mice and supplement the phagocytic activity of the pigment epithelium.We thank R.K. Hawkins for efficient management of the animal colony, H.G. Jansen for cooperation in the use of electron microscope and Ms Paula van Alphen for help in preparation of the illustrations.     

Activity of the reticuloendothelial system following exposure to electric stress and thymectomy

Summary After electric stress stimulation, granulopectic activity is reduced in otherwise normal rats, whereas it appears to be increased in thymectomized animals. The differences between the 2 groups of animals seem to support the hypothesis that the effects of stress upon the overall phagocytic capacity may be mediated by the products of lymphocyte breakdown.The collaboration of Prof. A. Colombi for the statistical analysis of the experimental results is gratefully acknowledged.     

Action of Corynebacterium parvum on the activity of glycosidases and proteases of peritoneal macrophages in the mice]

Glycosidase and peptidase of non-treated Mouse peritoneal macrophages were characterized. The enzymatic activities of Corynebacterium parvum stimulated Mouse macrophages were compared to those of macrophages obtained from non-treated animals. All the enzymatic activities, but beta-C-galactosidase, were higher in stimulated Mouse macrophages.     

Iron deposits in the chronically inflamed central nervous system and contributes to neurodegeneration

Neurodegenerative disorders are characterized by the presence of inflammation in areas with neuronal cell death and a regional increase in iron that exceeds what occurs during normal aging. The inflammatory process accompanying the neuronal degeneration involves glial cells of the central nervous system (CNS) and monocytes of the circulation that migrate into the CNS while transforming into phagocytic macrophages. This review outlines the possible mechanisms responsible for deposition of iron in neurodegenerative disorders with a main emphasis on how iron-containing monocytes may migrate into the CNS, transform into macrophages, and die out subsequently to their phagocytosis of damaged and dying neuronal cells. The dying macrophages may in turn release their iron, which enters the pool of labile iron to catalytically promote formation of free-radical-mediated stress and oxidative damage to adjacent cells, including neurons. Healthy neurons may also chronically acquire iron from the extracellular space as another principle mechanism for oxidative stress-mediated damage. Pharmacological handling of monocyte migration into the CNS combined with chelators that neutralize the effects of extracellular iron occurring due to the release from dying macrophages as well as intraneuronal chelation may denote good possibilities for reducing the deleterious consequences of iron deposition in the CNS.     

Phagocytic activity of the reticuloendothelial system in the rat after administration of an anticholinesterasic pesticide, carbaryl (author's transl)]

The effects of 4 carbaryl doses (0.375, 0.75, 1.50 and 3 mg/100 g) on the reticuloendothelial system (RES) phagocytic activity were studied 1 h after their administration to male rats. Carbaryl reduced RES phagocytic activity. Results showed a dose-dependent drop in RES phagocytic activity. Carbaryl might act as an inhibitor of phagocytes by saturing them to greater or lesser degree, depending on the dose administered.     

Uptake of exogenous protein by supraependymal cells of the feline area postrema.

Supraependymal cells occurring on the surface of the feline area postrema were examined for phagocytic ability. It was shown that they could ingest exogenous horseradish peroxidase that was experimentally introduced into the brain ventricular system. The cells thus bear functional as well as ultrastructural attributes of macrophages, similar to those found in the third ventricle and subarachnoid space.     

Activité phagocytaire du système réticuloendothélial du rat après administration d'un anticholinestérasique,le carbaryl

Summary The effects of 4 carbaryl doses (0.375, 0.75, 1.50 and 3 mg/100 g) on the reticuloendothelial system (RES) phagocytic activity were studied 1 h after their administration to male rats. Carbaryl reduced RES phagocytic activity. Results showed a dose-dependent drop in RES phagocytic activity. Carbaryl might act as an inhibitor of phagocytes by saturing them to greater or lesser degree, depending on the dose administered.     

Uptake of exogenous protein by supraependymal cells of the feline area postrema

Summary Supraependymal cells occurring on the surface of the feline area postrema were examined for phagocytic ability. It was shown that they could ingest exogenous horseradish peroxidase that was experimentally introduced into the brain ventricular system. The cells thus bear functional as well as ultrastructural attributes of macrophages, similar to those found in the third ventricle and subarachnoid space.We thank J. Stevens and A. Fenton for technical assistance. Supported by the Medical Research Council of Canada.     

Dietary vitamin E does not protect from endotoxin-induced hepatic microvascular dysfunction

Starting from the concept that lipopolysaccharide (LPS)-associated hepatotoxicity involves the action of reactive oxygen species, the present study was conducted to test whether vitamin E, a lipophilic antioxidant, prevents LPS-induced hepatic microvascular dysfunction and liver injury. Fifty-two rats were divided into three groups and fed diets containing 0 (n=16), 75 (n=18) or 8000 mg (n=18) α-tocopherol acetate/kg food for four weeks. At 1 h and 6 h after intravenous LPS-exposure (10 mg/kg E. coli LPS) hepatic microvascular response and liver injury were assessed by the analysis of Kupffer cell phagocytic activity, leukocyte-endothelial cell interaction and nutritive sinusoidal perfusion (intravital fluorescence epi- illumination technique) as well as bile flow, serum liver enzyme activities and tissue histomorphology. In animals fed with 75 mg vitamin E/kg (standard diet), LPS caused hepatic Kupffer cell activation (increased phagocytic activity) and hepatic microvascular leukocyte activation, with stasis in sinusoids and adherence in postsinusoidal venules (1 h) followed by leukocytic infiltration into tissue (6 h) and progredient sinusoidal perfusion failure (6 h). Hepatic microvascular injury was accompanied by reduced bile flow and enhanced liver enzyme release. Vitamin E-enriched diet (8000 mg/kg) and even vitamin E-deficient diet did not significantly affect LPS-induced hepatic microvascular cell activation and perfusion failure. Thus, we conclude, that vitamin E is not effective to protect from endotoxin-induced hepatic microvascular dysfunction. Received 7 November 1996; received after revision 30 December 1996; accepted 20 January 1997     

Effect of lead microparticles introduced into the respiratory system of the sensitivity of mice to Pasteurella multocida infection via aerosol]

Lead microparticles, resulting from the pyrolysis of organic lead used as an anti-knock agent in gasoline, were introduced into the lungs of Mice, during a short single exposure. When 6 microgram of lead were retained in the lungs (mean value per Mouse), the phagocytic ability of the pulmonary alveolar macrophages harvested 6 and 18 hrs. later, was significantly reduced. It was observed, in the same conditions, that the resistance of Mice to experimental infection by aerosolized Pasteurella multocida, was significantly reduced. When 3 microgram of lead were retained in the lungs, there was no significant difference between control and intoxicated Mice.     

Impairment of systemic DHA synthesis affects macrophage plasticity and polarization: implications for DHA supplementation during inflammation

Docosahexaenoic acid (DHA) is an omega-3 fatty acid obtained from the diet or synthesized from alpha-linolenic acid through the action of fatty acid elongases (ELOVL) and desaturases. DHA plays important roles in the central nervous system as well as in peripheral organs and is the precursor of several molecules that regulate resolution of inflammation. In the present study, we questioned whether impaired synthesis of DHA affected macrophage plasticity and polarization both in vitro and in vivo models. For this we investigated the activation status and inflammatory response of bone marrow-derived M1 and M2 macrophages obtained from mice deficient of Elovl2 (Elovl2^?/?), a key enzyme for DHA synthesis in mammals. Although both wild type and Elovl2^?/? mice were able to generate efficient M1 and M2 macrophages, M1 cells derived from Elovl2^?/? mice showed an increased expression of key markers (iNOS, CD86 and MARCO) and cytokines (IL-6, IL-12 and IL-23). However, M2 macrophages exhibited upregulated M1-like markers like CD80, CD86 and IL-6, concomitantly with a downregulation of their signature marker CD206. These effects were counteracted in cells obtained from DHA-supplemented animals. Finally, white adipose tissue of Elovl2^?/? mice presented an M1-like pro-inflammatory phenotype. Hence, impairment of systemic DHA synthesis delineates an alteration of M1/M2 macrophages both in vitro and in vivo, with M1 being hyperactive and more pro-inflammatory while M2 less protective, supporting the view that DHA has a key role in controlling the balance between pro- and anti-inflammatory processes.     

Radioprotective effect of a protein free parathyroid extract on the mitotic index of rat bone marrow cells.

The protective efficacy of an orally administered bovine protein-free parathyroid extract (PF-PTE) was studied on rat bone marrow cells in vivo with the mitotic index after 850 R irradiation. A remarkable decrease was found in the mitotic activity of bone marrow cells after irradiation in the non-protected animals. However, in the animals treated with PF-PTE after irradiation, a significantly smaller decrease and a faster recovery were found in the mitotic activity of the bone marrow cells.     

Heat-shock protein 60 translocates to the surface of apoptotic cells and differentiated megakaryocytes and stimulates phagocytosis

Heat-shock protein 60 (Hsp60) is a highly conserved stress protein which has chaperone functions in prokaryotes and mammalian cells. Hsp60 is associated with the mitochondria and the plasma membrane through phosphorylation by protein kinase A, and is incorporated into lipid membranes as a protein-folding chaperone. Its diverse intracellular chaperone functions include the secretion of proteins where it maintains the conformation of precursors and facilitates their translocation through the plasma membrane. We report here that Hsp60 is concentrated in apoptotic membrane blebs and translocates to the surface of cells undergoing apoptosis. Hsp60 is also enriched in platelets derived from terminally differentiated megakaryocytes and expressed at the surface of senescent platelets. Furthermore, the exposure of monocytic U937 cells to Hsp60 enhanced their phagocytic activity. Our results suggests that externalized Hsp60 in apoptotic cells and senescent platelets influences events subsequent to apoptosis, such as the clearance of apoptotic cells by phagocytes.     

Radioprotective effect of a protein free parathyroid extract on the mitotic index of rat bone marrow cells

Summary The protective efficacy of an orally administered bovine protein-free parathyroid extract (PF-PTE) was studied on rat bone marrow cells in vivo with the mitotic index after 850 R irradiation. A remarkable decrease was found in the mitotic activity of bone marrow cells after irradiation in the non-protected animals. However, in the animals treated with PF-PTE after irradiation, a significantly smaller decrease and a faster recovery were found in the mitotic activity of the bone marrow cells.     

Effect of trypsin,S-adenosylmethionine and ethionine on L-serine sulfhydrase activity

Summary Trypsin causes an activation of serine sulfhydrase in the liver extracts from intact animals, but inhibits enzyme activity in the liver of ethionine treated rats. Trypsin also decreases an elevation of serine sulfhydrase activity caused by S-adenosylmethionine.This work was supported by the Serbian Medical Research Foundation.     

Stimulation und Depression der Phagozytoseaktivität des retikulo-endothelialen Systems nach Röntgenbestrahlung

Summary The effect of X-irradiation on the phagocytic activity of the RES depends on the carbon dose. Using small doses a stimulation was found; this indicates an increased velocity of carbon uptake by the phagocytes. Using high doses a depression was found indicating a decreased phagocytic capacity of the cells.     

Factor XIII subunit A as an intracellular transglutaminase

Over the last 2 decades there has been increasing evidence that the role of factor XIII (FXIII) is not restricted to the area of hemostasis and that its subunit A functions as an intracellular enzyme in platelets and monocytes/macrophages. FXIII is already expressed during compartmentalisation of the precursors of megakaryocyte/platelet and monocyte/macrophage cell lines in the bone marrow. FXIII-A, produced by megakaryocytes, is packaged into budding platelets and is present in huge quantity in circulating ones. It seems very likely that it plays an important role in the cytoskeletal remodelling associated with the activation stages of platelets. FXIII-A can also be detected in blood monocytes and in all subsets of monocyte-derived macrophages throughout the body. FXIII-A is mainly localised in the cytoplasm, in association with cytoskeletal filaments, but at a relatively early stage of macrophage differentiation it also appears transiently in the nucleus. Cytoplasmic expression has a very close relationship with phagocytic activities. Further research is needed to understand the biological significance of its nuclear presentation.