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PubMed2004

Regulation of differentiation and functional properties of monocytes and monocyte-derived dendritic cells by interferon beta in multiple sclerosis.

Interferon beta (IFN beta) has complex immune regulatory properties that contribute to its treatment effect on multiple sclerosis (MS). In this study, we investigated the role of IFN beta in differentiation and functional properties of monocytes and monocyte-derived dendritic cells that are critical to the inflammatory process in MS. The results revealed that IFN beta inhibited intracellular production of interleukin (IL)-1b (P<0.01) in both monocytes exposed to in vitro treatment of IFN beta and monocytes analysed ex vivo from MS patients treated with IFN beta. IFN beta was shown to modulate differentiation of monocytes into dendritic cells in the presence of IL-4 and GM-CSF, which resulted in a delayed differentiation process. Furthermore, it characteristically altered the phenotypic features of differentiated dendritic cells by inhibiting the expression of CD1a, CD11b, CD11c, CD123 and CD209 while upregulating costimulatory molecules, such as CD86. The selective regulatory properties of IFN beta appeared to render the function of differentiated dendritic cells to produce an increased amount (P<0.01) while their ability to secrete proinflammatory IL-12 and TGF beta was significantly reduced. The observed collective effects of IFN beta seemed to correlate with Th2 immune deviation. The study has provided new insights into the regulatory mechanisms of IFN beta in the treatment of MS.

Adjuvants, Immunologic↗
PubMed1992

Expression of monocyte activation antigen Mo3 on the surface of peripheral blood monocytes from patients with multiple sclerosis.

Exposure of human peripheral blood monocytes (PBM) to phorbol esters, bacterial products, and cyclic adenosine monophosphate agonists is known to stimulate expression of a plasma membrane antigen ([Ag]; Mo3). Mo3 is recognized by two monoclonal antibodies, Mo3e (IgM), and Mo3f (IgG). Surface Mo3 is barely detectable by indirect immunofluorescence flow cytometry in nonstimulated monocytes. Mo3-positive monocytes have been found in inflammatory tissues, but increased surface expression of Mo3 in PBM has not been seen in any patient group. We report that PBM from patients with chronic progressive MS (CPMS) express increased Mo3. PBM from patients with other neurologic diseases and healthy controls express little measurable Mo3. No difference was seen in class II major histocompatibility complex Ag expression and in Mo2 (CD14) expression. Exposure of PBM to lipopolysaccharide (10 mg/ml) enhanced Mo3 expression in both MS patients and controls. Mo3 expression on CPMS PBM was not dependent on culture conditions. Taken together, our observations suggest that monocytes from patients with MS are stimulated in vivo to express activation Ag Mo3, but that Mo3-positive monocytes need not be upregulated for HLA-DR.

Cell Separation↗
PubMed1987

Halothane anesthesia decreases human monocyte hydrogen peroxide generation. Protection of monocytes by activation with gamma interferon.

In an effort to determine the impact of halothane anesthesia on certain human cell-mediated immune functions, normal, purified human monocytes and lymphocytes were exposed to halothane in vitro at varying concentrations for up to 8 hours. Subsequently, these human effector cells were analyzed for their ability to function in several cell-mediated immunologic assays. Natural killer cell activity against K-562 was unaffected by halothane in most of the donors tested. Similarly, the ability of purified monocytes to inhibit MBL-2 tumor cell growth was unchanged. Halothane appeared to decrease the proliferative response of lymphocytes to phytohemagglutinin (PHA) in approximately 50% of the normal donors tested. In contrast, the ability of monocytes to lyse antibody-coated red cell targets (ADCC) was unaffected by even maximal exposure to halothane. Of interest was the finding that human monocytes exposed to as low as 2% halothane anesthesia for 4 hours displayed a dramatic down-regulation of hydrogen peroxide (H2O2) release. Since it is known that hydrogen peroxide and other incompletely reduced forms of oxygen secreted by monocytes can play a major role in the antimicrobial, antitumor, and inflammatory functions of these cells, this finding may help explain the enhanced susceptibility of post-operative patients to infections.

Adult↗
PubMed2001

Low-level monocyte chemoattractant protein-1 stimulation of monocytes leads to tumor formation in nontumorigenic melanoma cells.

Tumors commonly produce chemokines for recruitment of host cells, but the biological significance of tumor-infiltrating inflammatory cells, such as monocytes/macrophages, for disease outcome is not clear. Here, we show that all of 30 melanoma cell lines secreted monocyte chemoattractant protein-1 (MCP-1), whereas normal melanocytes did not. When low MCP-1-producing melanoma cells from a biologically early, nontumorigenic stage were transduced to overexpress the MCP-1 gene, tumor formation depended on the level of chemokine secretion and monocyte infiltration; low-level MCP-1 secretion with modest monocyte infiltration resulted in tumor formation, whereas high secretion was associated with massive monocyte/macrophage infiltration into the tumor mass, leading to its destruction within a few days after injection into mice. Tumor growth stimulated by monocytes/macrophages was due to increased angiogenesis. Vessel formation in vitro was inhibited with mAbs against TNF-alpha, which, when secreted by cocultures of melanoma cells with human monocytes, induced endothelial cells under collagen gels to form branching, tubular structures. These studies demonstrate that the biological effects of tumor-derived MCP-1 are biphasic, depending on the level of secretion. This correlates with the degree of monocytic cell infiltration, which results in increased tumor vascularization and TNF-alpha production.

Animals↗
PubMed2003

Differentiation of monocytic cell clones into CD8 alpha+ dendritic cells (DC) suggests that monocytes can be direct precursors for both CD8 alpha+ and CD8 alpha- DC in the mouse.

Dendritic cells (DC) are the professional APCs that initiate T cell immune responses. DC can develop from both myeloid and lymphoid progenitors. In the mouse, the CD8alpha(+) DC had been designated as "lymphoid" DC, and CD8alpha(-) DC as "myeloid" DC until recently when it was demonstrated that common myeloid progenitors can also give rise to CD8alpha(+) DC in bone marrow chimera mice. However, it is still not clear which committed myeloid lineages differentiate into CD8alpha(+) DC. Because monocytes can differentiate into DC in vivo, the simplest hypothesis is that the CD8alpha(+) DC can be derived from the monocyte/macrophage. In this study we show that cell clones, isolated from CD8alpha(+) DC lymphoma but with a monocytic phenotype (CD11c(low/-)D11b(high)CD8alpha(-)I-A(low)), can redifferentiate into CD8alpha(+) DC either when stimulated by LPS and CD40L or when they migrate into the lymphoid organs. Maturation of DC in vivo correlated with strong priming of allogeneic T cells. Moreover, the monocytes from cultured splenocytes or peritoneal exudates macrophages of wild-type mice are also capable of differentiating into CD11c(+)CD8alpha(+) DC after their migration into the draining lymph nodes. Our results suggest that monocytes can be direct precursors for CD11c(+)CD8alpha(+) DC in vivo. In addition, the monocyte clones described in this study may be valuable for studying the differentiation and function of CD8alpha(+) DC that mediate cross-presentation of Ag to CD8 T cells specific for cell-associate Ags.

3T3 Cells↗
PubMed2004

Soluble fractalkine prevents monocyte chemoattractant protein-1-induced monocyte migration via inhibition of stress-activated protein kinase 2/p38 and matrix metalloproteinase activities.

In this study, we address the question of the cross-talk between two chemokines that are cosecreted during inflammation, namely monocyte chemoattractant protein-1 (MCP-1) and soluble fractalkine (s-FKN), toward monocyte migration. We found that s-FKN fails to induce MonoMac6 cell migration per se. Interestingly, this chemokine antagonizes transendothelial migration and chemotaxis of MonoMac6 cells and freshly isolated human monocytes induced by MCP-1, indicating a direct effect of s-FKN on monocytic cells. In this study, we found that stress-activated protein kinase (SAPK)1/c-Jun N-terminal kinase 1 and SAPK2/p38 are involved in the control of MCP-1-induced MonoMac6 cell migration. We demonstrated that s-FKN abrogates the MCP-1-induced SAPK2/p38 activation as well as the upstream Pyk2 activity. Furthermore, we observed that s-FKN also inhibits the activity of a major matrix metalloproteinase (MMP), namely MMP-2. Taken collectively, our results indicate that the s-FKN antagonizes the chemoattractant effect of MCP-1 on monocytes, likely by inhibiting crucial signaling pathways, like SAPK2/p38 and MMP-2 activities.

Cell Line↗
PubMed1999

Increased expression of u-PA and u-PAR on monocytes by LDL and Lp(a) lipoproteins--consequences for plasmin generation and monocyte adhesion.

Monocyte-derived foam cells figure prominently in rupture-prone regions of atherosclerotic plaque. As urokinase/urokinase-receptor (u-PA/u-PAR) is the trigger of a proteolytic cascade responsible for ECM degradation, we have examined the effect of atherogenic lipoproteins on monocyte surface expression of u-PAR and u-PA. Peripheral blood monocytes, isolated from 10 healthy volunteers, were incubated with 10 to 200 microg/ml of native or oxidised (ox-) atherogenous lipoproteins for 18 h and cell surface expression of u-PA and u-PAR was analysed by flow cytometry. Both LDL and Lp(a) induced a dose-dependent increase in u-PA (1.6-fold increase with 200 microg/ml of ox-LDL) and u-PAR [1.7-fold increase with 200 microg/ml of ox-Lp(a)]. There is a great variability of the response among the donors, some of them remaining non-responders (absence of increase of u-PA or u-PAR) even at 200 microg/ml of lipoproteins. In positive responders, enhanced u-PA/u-PAR is associated with a significant increase of plasmin generation ( .9-fold increase with 200 microg/ml of ox-LDL), as determined by an amidolytic assay. Furthermore, monocyte adhesion to vitronectin and fibrinogen was significantly enhanced by the lipoproteins [respectively 2-fold and 1.7-fold increase with 200 microg/ml of ox-Lp(a)], due to the increase of micro-PAR and ICAM-1, which are receptors for vitronectin and fibrinogen. These data suggest that atherogenous lipoproteins could contribute to the development of atheromatous plaque by increasing monocyte adhesion and trigger plaque weakening by inducing ECM degradation.

Cell Adhesion↗
PubMed2001

Gene expression of monocyte chemoattractant protein-1 in human monocytes by exposure to advanced glycosylation end products.

AIM: To explore the effects of advanced glycosylation end products (AGEP) on monocyte chemoattractant protein-1 (MCP-1) gene expression in human peripheral blood monocytes/macrophages (PBMC). METHODS: Expression of MCP-1 mRNA in PBMC incubated with AGEP-bovine serum albumin (AGEP-BSA) was examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) with beta-actin as an internal standard. Sequencing of RT-PCR products was performed to confirm the specificity of amplification for MCP-1 gene. RESULTS: AGEP-BSA stimulated monocytes to express MCP-1 mRNA in a glucose-concentration-related fashion. The levels of MCP-1 mRNA were increased slightly when monocytes were exposed to AGEP-BSA 200 mg/L (glycosylated with glucose 20 mmol/L), and increased markedly when exposed to AGEP-BSA 200 mg/L (glycosylated with glucose 50 mmol/L), but decreased slightly when exposed to AGEP-BSA 200 mg/L (glycosylated with glucose 80 mmol/L). Expression of MCP-1 mRNA was undetectable in freshly isolated monocytes, but was induced at 12 h and reached a maximal level at 24 h and was almost undetectable at 36 h after the monocytes were incubated with AGEP-BSA 200 mg/L (P < 0.01). CONCLUSION: AGEP enhanced MCP-1 mRNA expression in human PBMC.

Cells, Cultured↗
PubMed2002

[Increased expression of monocytic cell adhesion molecules and formation of monocyte-thrombocyte aggregates in coronary restenosis].

AIM: To examine expression of superficial antigens by blood monocytes and granulocytes as well as the number of leukocyte-platelet complexes forming in in vitro activation in patients subjected to coronary angioplasty; to analyse changes in these parameters in coronary restenosis. MATERIAL AND METHODS: Membrane expression of leukocytic antigens and the number of leukocyte-platelet complexes after activation in the whole blood were measured by direct immunofluorescence and flow cytometry in 24 patients who have undergone stenting of coronary arteries. 14 of them had angiographically confirmed restenosis. RESULTS: The tests discovered high expression of integrins Mac-1 and VLA-4 by monocytes and elevated relative number of monocyte-platelet complexes in patients with restenosis vs those free of stenosis (1425 +/- 76 and 1195 +/- 71 r.u. for Mac-1, 87 +/- 7 and 65 +/- 6 r.u. for VLA-4, 47 +/- 4 and 29 +/- 3%, respectively, for monocyte-platelet complexes; p < 0.05 for all the indices). CONCLUSION: Coronary restenosis may result from elevated expression of adhesion molecules by monocytes manifest in activation of the cells in vitro.

Angioplasty, Balloon, Coronary↗
PubMedDate not supplied

Effects of alpha- and beta-interferon on oxidative burst responses of monocytes and monocyte-derived macrophages from patients with HIV infection.

In the present paper, we have studied the effects of interferon (IFN) -alpha and IFN-beta on the oxidative burst (OB) responses in monocytes and monocyte-derived macrophages from patients with a relatively early phase of HIV infection. We found that in monocytes from patients with HIV infection, the defective OB response could be partially restored by pretreatment with IFN-beta when the cells were challenged with zymosan. No such stimulatory effect was seen in the control groups. In monocyte-derived macrophages, both IFN-alpha and IFN-beta stimulated the phorbol myristate acetate (PMA) induced OB response in the patient group as well as in the blood donor control group. Generation of an OB is an important part of the antimicrobial defence of mononuclear phagocytes. The positive effects of IFN on the OB responses of monocytes and macrophages from patients with HIV infection may be of importance when IFNs are considered in the treatment of HIV-related disease.

Cells, Cultured↗
PubMed1990

Identification of high affinity receptors for human monocyte chemoattractant protein-1 on human monocytes.

The binding of human monocyte chemoattractant protein-1 (MCP-1) to human monocytes was studied. MCP-1 was radioiodinated with Iodo-beads (Pierce Chemical Co., Rockford, IL) without significant loss of biologic activity. 125I-MCP-1 binding to PBMC occurred within 5 min at 0 degrees C and the binding was inhibited by unlabeled MCP-1 dose dependently but not by neutrophil attractant/activation protein-1 or FMLP. 125I-MCP-1 bound to monocytes; no significant binding to either neutrophils or lymphocytes was observed. Scatchard plot analysis indicated that monocytes had a minimum of 1700 +/- 600 binding sites per cell with a Kd of 1.9 +/- 0.2 x 10(-9) M. For analysis of binding by flow cytometry, MCP-1 was biotinylated. In contrast to radioiodination, biotinylation resulted in loss of activity; potency was 10-fold less, but the efficacy was retained. Detection by flow cytometry of bound biotinylated MCP-1 with avidin-FITC confirmed results obtained with 125I-MCP-1. Biotinylated MCP-1 bound to monocytes but not to lymphocytes; and the binding was inhibited by a 100-fold excess of unlabeled MCP-1.

Chemokine CCL2↗
PubMed1986

Intracellular localization of human monocyte associated interleukin 1 (IL 1) activity and release of biologically active IL 1 from monocytes by trypsin and plasmin.

The production of interleukin (IL 1) by normal human peripheral blood monocytes purified by Ficoll-Hypaque density sedimentation, Percoll-gradient sedimentation, and plastic adherence can be detected as early as 30 min intracellularly, and extracellularly within 1 hr after stimulation with lipopolysaccharide (LPS). Production of mRNA coding for the isoelectric point 7.0 species of IL 1 was also detected as early as 1 hr after LPS stimulation and reached a maximum level at 6 hr. Cell-associated IL 1 activity could be extracted with CHAPS detergent from every cell fraction (i.e., membranes, cytosol, and particulates), but was present mainly (greater than 95%) in the cytosol of LPS-activated monocytes and the myelomonocytic cell line, THP-1. The apparent m.w. of IL 1 activity on high pressure liquid chromatography gel filtration in every cell fraction was approximately 23,000 daltons, with a minor peak at 31,000 daltons, whereas the IL 1 activity in the culture supernatants was 17,000 daltons. Western blotting analysis of LPS-stimulated monocyte extracts showed two forms of IL 1 corresponding to 31,000 daltons and 25,000 daltons. Exposure of viable cells to trypsin and plasmin released biologically active 23,000 dalton IL 1 only from IL 1-producing cells such as activated monocytes and IL 1-producing Ebstein-Barr virus B lymphocyte cell lines. Consequently, biologically active IL 1 is presumably exposed on the outer surface of cell membranes. Furthermore, IL 1 release by human monocytes in plasminogen-depleted fetal calf serum was considerably decreased. Conversely, supplementation of plasminogen-depleted serum with purified plasminogen restored the IL 1 production, suggesting that plasmin or plasmin-like factors may be involved in the regulation of the release of IL 1 from IL 1-producing cells. In conclusion, the results suggest that IL 1 is rapidly produced, is pooled in the cytosol, and in part is processed by enzymes, is transferred to the plasma membranes, and is then released from the cells. Tissue plasminogen activator and serum enzymes such as plasmin may therefore be involved in the release of IL 1 from IL 1-producing cells.

Body Fluids↗
PubMed1989

[A light and electron microscopic study of acute myelomonocytic leukemia cells in comparison with normal monocytes and acute monocytic leukemia cells].

Leukemic cells from 15 patients with acute myelomonocytic leukemia (M4) were investigated by light and electron microscopy. As controls, the blood cells from 2 normal volunteers and 3 acute monocytic leukemia (M5b) were examined. To identify monocytic cells, a double esterase (DE) staining combining with alpha-naphthyl butyrate esterase (ANBE) and naphthol-ASD chloroacetate esterase (N-ASD-CAE) stainings was used. According to DE staining, M4 leukemic cells were classified into ANBE positive cells, N-ASD-CAE positive cells and DE-positive cells coated vesides. Ultrastructurally, M4 leukemic cells possessed indented nuclear membrane, clusters of myeloperoxidase-positive rod-like granules, coated vesicles, abundant smooth endoplasmic vesicles and invaginated cell membrane similarly to M5b leukemic cells and normal monocytes. These features were observed not only in the ANBE positive cells but also in the DE-positive cells. The N-ASD-CAE positive cells in M4 ultrastructurally showed atypical features of polymorphonuclear leukocytes and possessed monocytic characteristics to some extents. M4 leukemic cells occasionally showed some peculiar structures such as the reticulated lamellae complex, paired cisternae and annulate lamellae. The cells showing erythrophagocytosis were either observed. Combining the results of DE staining and electron microscopy, it was suggested that M4 is closely associated with the malignant transformation of a monocyte/granulocyte precursor cell which has an ability to differentiate to both monocyte and granulocyte.

Adult↗
PubMed1985

The characteristics of binding of human recombinant interferon-gamma to its receptor on human monocytes and human monocyte-like cell lines.

Interferon-gamma (IFN-gamma) induces many effector functions in macrophages, presumably through binding to cell surface receptors. Such receptors have been documented in murine macrophages. This report demonstrates that IFN-gamma interacts with a specific receptor on human monocytes and monocyte-like cell lines, U937 and HL60. Recombinant IFN-gamma (rIFN-gamma) was radioiodinated by using Bolton-Hunter reagent to high specific activity. 125I-rIFN-gamma bound in a specific and saturable manner. Saturation of binding sites occurred at 10(-9) M (300 U/ml); there were 4000 specific binding sites per cell for both monocytes and the cell lines. Purified lymphocyte-derived IFN-gamma as well as rIFN-gamma competed for binding sites with 125I-rIFN-gamma. There was no inhibition of binding of the 125I-rIFN-gamma by rIFN-alpha or rIFN-beta. The forward rate constant, k1, at 4 degrees C was about 8 X 10(5) M-1 sec-1 for each cell type studied. In the presence of excess ligand, the dissociation rate constant, k-1, was about 2 X 10(-4) sec-1. The Ka calculated from these constants (4 X 10(9) M-1) agreed closely with that calculated from experiments performed at equilibrium (8 X 10(9) M-1). Because the dissociation of rIFN-gamma from cells was enhanced in the presence of ligand, interactions between binding sites of a negative cooperative type could be operative. These studies demonstrate that rIFN-gamma binds in a specific and saturable manner and with high affinity to a receptor on human monocytes as well as monocyte-like cell lines.

Binding Sites↗
PubMed1979

Long-term human peripheral blood monocyte cultures: establishment, metabolism and morphology of primary human monocyte-macrophage cell cultures.

Human peripheral blood monocytes were maintained in in vitro culture for periods up to 4 months using a non-human serum source. Monocytes were cultured in Dulbecco's modified Eagle's medium buffered with 20 mM HEPES and containing 10% horse serum and 10% foetal calf serum. The metabolic and morphological changes which occur in vitro were investigated using microtitre, Linbro and T 25 cultures. During culture, monocytes increased in size, had increased membrane activity as visualized by SEM, and differentiated into a morphologically heterogeneous population of fusiform and epithelioid shapes. These cell types retained the ability to phagocytose E glut and EA and to rosette with EA and EAC. Larger giant polynucleated cells were also observed during culture; many of these lacked the ability to bind or phagocytose inert or antibody-coated erythrocytes. Increases in lysozyme release and acid phosphatase activity also occurred during culture. Cultured monocytes exhibited characteristic profiles of leucine and uridine uptake with maximal activity observed by 5 days of culture. There was no detectable uptake of thymidine. Detailed analysis of regulatory processes involved in monocyte growth and differentiation could be performed with this in vitro system.

Cells, Cultured↗
PubMed1985

Development of specific surface receptors recognizing mannose-terminal glycoconjugates in cultured monocytes: a possible early marker for differentiation of monocyte into macrophage.

Surface receptors for mannose-terminal glycoconjugates have been reported in various macrophage populations and are thought to be involved in specific binding and internalization of mannose-rich substances. They thereby may serve a function in such phenomena as phagocytosis of yeast and tumor cell recognition. Little is known of mannosyl receptors in blood monocytes. We synthesized a probe by covalently linking D-mannose to bovine serum albumin (BSA). Using this probe in fluoresceinated or latex minibead-derivatized forms, we searched the surface of human monocytes for the presence of mannosyl receptors. 125I-labeled probe was further used to quantify the number of receptors and the kinetics of the binding. Freshly isolated monocytes did not bind the probe, indicating the absence of mannosyl receptors. When placed in a culture system that preserves functional and morphological homogeneity of the cells, surface receptors for D-mannosyl glycoproteins developed within four days, reached a peak after one week, and then remained fairly stable. Binding parameters (Kd, Bmax, and receptor number) also remained stable and were not dissimilar to those reported for macrophages, although the Kd was consistently larger in cultured monocytes. When studied at 37 degrees C, the ligand-receptor complex was internalized through a system of coated pits and vesicles. The development of these receptors before evidence of morphological or functional differentiation suggests that these receptors may constitute an early marker for differentiation of monocytes into macrophages.

Cell Differentiation↗
PubMed1979

Humoral and formed elements of blood modulate the response of peripheral blood monocytes. I. Plasma and serum inhibit and platelets enhance monocyte adherence.

Human and rabbit peripheral blood monocytes normally adhere to plastic tissue culture plates in vitro when they are suspended in Hanks' media. Increasing amounts of autologous serum or heat-inactivated plasma in the cell suspensions prevented the adherence of both monocytes and lymphocytes. The inhibitory effect of plasma was separated into three areas of activity by chromatography on Sephacryl S-200. The profile of inhibitory activity did not coincide with the protein elution profile, suggesting that inhibition was not a nonspecific protein effect. A layer of adherent platelets overcame the inhibitory effect of plasma on monocyte adherence. Platelets selectively increased monocyte as opposed to lymphocyte adherence and this was specific for platelets in that neither neutrophils nor fibroblasts could substitute for platelets. Both plasma and platelets acted directly on monocytes.

Animals↗
PubMed1979

Transformation of monocytes into amoeboid microglia in the corpus callosum of postnatal rats, as shown by labelling monocytes by carbon particles.

Two successive intravenous doses of carbon suspension were given at 24 hourly intervals into six days old rats. These animals were killed at intervals ranging from 1 to 9 days after the second injection. The corpus callosum and neighbouring structures were examined for cells containing ingested colloidal carbon particles in their cytoplasm. Twenty four hours after the second injection, a variable number of carbon-labelled monocytes were adherent to the luminal wall of blood vessels in the corpus callosum. Numerous carbon-labelled cells appeared to have left the lumen and entered the brain tissue surrounding the vessels. These perivascular carbon-labelled monocytes in the neuropil displayed a large pale nucleus with fine chromatin granules. The phagocytic amoeboid microglia in the corpus callosum were unlabelled at first, although a few cells of a similar nature in the cavum septi pellucidi did show carbon particles in their cytoplasm. Four or five days after the second carbon injection perivascular carbon-labelled monocytes were rare, but carbon particles were now present in the amoeboid microglia. At 8 days amoeboid microglia were virtually absent from the corpus callosum but carbon particles now appeared in cells which closely resembled microglia (flattened nucleus, coarse chromatin, scanty cytoplasm at one pole). The sequential appearance of carbon particles in monocytes, amoeboid microglia, and microglia, suggests that monocytes transform into microglia by way of an amoeboid microglial stage.

Aging↗