Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MACROPHAGES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed2006

Granulocyte-macrophage colony-stimulating factor inhalation therapy for patients with idiopathic pulmonary alveolar proteinosis: a pilot study; and long-term treatment with aerosolized granulocyte-macrophage colony-stimulating factor: a case report.

Idiopathic pulmonary alveolar proteinosis (IPAP) is considered to be caused by an autoantibody to the granulocyte-macrophage colony-stimulating factor (GM-CSF), which neutralizes GM-CSF and therefore impairs the differentiation of alveolar macrophages. The authors have previously characterized the BAL fluid and alveolar macrophages obtained from three IPAP patients who were successfully treated with aerosolized GM-CSF and demonstrated restoration of the cell number, expression of surface marker, and phagocytic ability of the alveolar macrophages as well as a decrease in the autoantibody levels in the BAL fluid. The condition recurred in one of the patients after 20 months. This patient underwent a second and third course of GM-CSF inhalation therapy with the same dose and schedule as the first one. Since the second therapeutic intervention did not succeed in producing any improvement in the symptoms and disease markers, the authors used a new nebulizer and a liquid preparation of the drug instead of the lyophilized preparation for the third therapeutic session and this restored the respiratory function considerably. A 6-month maintenance therapeutic regimen with a lower GM-CSF inhalation frequency brought about a further improvement in the disease markers. The results suggest that the efficacy of GM-CSF inhalation therapy might be related to the drug preparation mode, choice of nebulizer, and duration of treatment.

Aerosols↗
PubMed1993

MDHM, a macrophage-activating product of Mycoplasma fermentans, stimulates murine macrophages to synthesize nitric oxide and become tumoricidal.

In continuation of previous work on macrophage activation by a Mycoplasma fermentans-derived product, originally named "mycoplasma-derived high mol. wt. material" (MDHM), we have investigated whether MDHM was capable of inducing synthesis of the reactive nitrogen intermediate nitric oxide (NO), thus rendering macrophages cytocidal. Mycoplasmas were first delipidated with acetone, and MDHM activity was then extracted with 50 mM 1-O-octyl-beta-D-glucopyranoside to yield a particularly active new preparation of MDHM which we have named MDHM-D (D for detergent). In combination with IFN-gamma, MDHM-D activated macrophages to produce reactive nitrogen intermediates and kill P815 mastocytoma cells in co-culture. P815 target cells were chosen because they are TNF-resistant. Macrophages from the LPS-low responder strain C3H/HeJ were used to minimize interference from possible LPS contamination. MDHM-D activity in this system was strictly IFN-gamma-dependent. In the presence of 25 U/ml IFN-gamma MDHM-D gave a half maximal response at a dilution of 1/100,000, showing a parallel concentration dependency for nitrite production and cytocidal activity.

Animals↗
PubMed1977

Interactions between salmonellae and macrophages of guinea pigs. IV. Relationship between migration inhibition and antibacterial action of macrophages.

The in vitro macrophage migration inhibition test was used to detect the development of delayed-type hypersensitivity in guinea pigs infected with Salmonella typhimurium. Four different preparations from supernatants of S. typhimurium cultures were used as the antigens in this test. They included the concentrated bacterial antigens, the high-molecular-weight (>50,000) antigens, the ammonium sulfate-precipitated antigens, and the ribonuclease-treated antigens. All four antigen preparations were shown to inhibit the migration of peritoneal macrophages of salmonella-infected (immune) guinea pigs from capillary tubes, in comparison with cells of normal control animals. By use of the high-molecular-weight antigens and the ammonium sulfate-precipitated antigens, the production of the migration inhibition factor(s) was elicited from cultures of lymphocytes obtained from the peripheral blood of immune guinea pigs. The activity of the migration inhibition factor(s) was demonstrated by its ability to inhibit the migration of peritoneal macrophages of normal guinea pigs from capillary tubes. In contrast, normal peritoneal macrophages exposed to products of antigen-stimulated immune lymphocytes did not exhibit an enhanced phagocytic or bactericidal action against virulent S. typhimurium as compared with those of the normal control. The present study indicated that the bacterial antigens responsible for the elicitation of the production of the migration inhibition factor from lymphocytes of immune guinea pigs are inactivated by proteolytic enzymes, but not by ribonuclease, and have molecular weights of >50,000.

Animals↗
PubMed1995

Enhancement of macrophage microbicidal activity: supplemental arginine and citrulline augment nitric oxide production in murine peritoneal macrophages and promote intracellular killing of Trypanosoma cruzi.

The generation of nitric oxide (NO) is largely responsible for the intracellular killing of Trypanosoma cruzi by activated macrophages. The present study was carried out to determine whether the production of NO by activated murine macrophages cultured in physiologic levels of arginine can be augmented by increasing the availability of arginine, the substrate for NO biosynthesis. Increased exogenous arginine or citrulline resulted in a significant increase in NO production and complete clearance of the parasites by activated macrophages. As citrulline fully substituted for arginine in supporting NO production and trypanocidal activity, these results demonstrate the expression of a highly active citrulline-NO cycle in activated macrophages and that levels of arginine in plasma are limiting with respect to both NO production and trypanocidal activity in these cells. The results indicate that increasing plasma substrate levels for both arginine and NO biosynthesis may represent a means of enhancing microbicidal activity in vivo.

Animals↗
PubMed2006

Tubulointerstitial macrophage accumulation is regulated by sequentially expressed osteopontin and macrophage colony-stimulating factor: implication for the role of atorvastatin.

Infiltration and local proliferation are known factors that contribute to tubulointerstitial macrophage accumulation. This study explored the time course of these two contributors' roles as tubulointerstitial inflammation and fibrosis progressing, and evaluated the mechanisms of the protective effect of atorvastatin. Unilateral ureteral obstructive (UUO) rats were treated with atorvastatin (10 mg/Kg) or vehicle. Expression of osteopontin (OPN) and macrophage colony-stimulating factor (M-CSF) was evaluated by RT-PCR and immunohistochemistry. Immunohistochemistry staining of ED1 was used to assess macrophage accumulation in interstitium. Histological evaluation was performed to semiquantify tubulointerstitial fibrosis. The results showed that on day 3 after UUO operation, OPN expression significantly increased and positively correlated with the number of the interstitial ED1(+) cells, while on day 10, M-CSF expression upregulated and correlated with interstitial ED1(+) cells. In atorvastatin treatment group, the increments of these two factors were attenuated significantly at the two time points, respectively. ED1(+) cell accumulation and fibrosis also ameliorated in the treatment group. For all the samples of UUO and treatment group on day 10, ED1(+) cells also correlated with interstitial fibrosis scores. The results suggest that OPN may induce the early macrophage/monocyte infiltration and M-CSF may play an important role in regulating macrophage accumulation in later stage of UUO nephropathy. Statin treatment decreases interstitial inflammation and fibrosis, and this renoprotective effect may be mediated by downregulating the expression of OPN and M-CSF.

Animals↗
PubMed2006

Normoxic stabilization of hypoxia-inducible factor-1alpha by modulation of the labile iron pool in differentiating U937 macrophages: effect of natural resistance-associated macrophage protein 1.

Hypoxia-inducible factor (HIF) is a transcription factor with major roles in many cellular and systemic responses to hypoxia. Activation of HIF pathways under hypoxia is mediated by suppression of the Fe(2+)- and O(2)-dependent HIF hydroxylase enzymes that normally inactivate HIFalpha subunits. Mechanisms underlying induction of HIF in normoxic conditions are less clearly understood. In human cancers, infiltrating macrophages show up-regulation of HIF and it has recently been shown that normoxic expression of HIF-1alpha is essential for macrophage function. Here, we report studies of HIF-1alpha induction following phorbol-12-myristate 13-acetate (PMA)-induced differentiation of monocytic U937 and THP1 cells. HIF-1alpha was markedly up-regulated under normoxia in this setting and this involved failure of HIF-1alpha prolyl hydroxylation despite the presence of O(2). Fluorescence measurements showed that differentiation was associated with marked reduction of the labile iron pool. Both the reduction in labile iron pool and the up-regulation of HIF-1alpha were suppressed by RNA interference-mediated down-regulation of the iron transporter natural resistance-associated macrophage protein 1. Up-regulation of HIF-1alpha following PMA-induced differentiation was also abolished by addition of Fe(2+) or ascorbate. These results indicate that physiologic changes in macrophage iron metabolism have an important effect on HIF hydroxylase pathways and suggest means by which the system could be manipulated for therapeutic benefit.

Ascorbic Acid↗
PubMedDate not supplied

A macrophage-tropic HIV-1 that expresses green fluorescent protein and infects alveolar and blood monocyte-derived macrophages.

We describe the construction of a macrophage-tropic HIV-1 molecular clone, pNLAD8-EGFP, which expresses enhanced green fluorescent protein. We show that NLAD8-EGFP can infect monocyte-derived macrophages as well as alveolar macrophages. NLAD8-EGFP-infected macrophages can be easily and sensitively detected based on the visualization of intracellular green fluorescent protein.

Giant Cells↗
PubMed1982

Tumor-promoting diterpene esters prevent macrophage activation and suppress macrophage tumoricidal capacity.

The efficacy of varied diterpene ester type tumor promoters in suppressing the acquisition as well as the manifestation of cytolytic activity by macrophages was investigated. These mechanisms, believed to be basic to natural antitumor resistance, were markedly suppressed not only by the phorbol ester, TPA, but also by several other tumor promoters of the polyfunctional diterpene ester type covering tigliane, ingenane, and daphnane derivatives. The promoters were particularly effective in preventing the lymphokine-induced enhancement of natural cytolytic activity in resting macrophages. Moreover, the same promoters suppressed the manifestation of cytotoxicity by previously activated macrophages. Their influence on the effector phase was less pronounced than on the activation phase. In sharp contrast, typical solitary carcinogens of the polycyclic aromatic hydrocarbon type exerted little or no activity in the macrophage test systems. Since TPA had already been shown to suppress the natural killer activity in vitro and to abrogate host tumor resistance in vivo, the present findings lend further support to the interpretation that tumor promoters, apart from directly stimulating the outgrowth of transformed cells, may function via interference with natural antitumor effector systems.

Animals↗
PubMed1987

Hydrogen peroxide release by alveolar macrophages from sarcoid patients and by alveolar macrophages from normals after exposure to recombinant interferons alpha A, beta, and gamma and 1,25-dihydroxyvitamin D3.

We measured H2O2 release by human alveolar macrophages (AM) from normals and sarcoid patients in suspension immediately after bronchoalveolar lavage in the presence and absence of the triggering agent, phorbol myristate acetate (PMA). AM from 11 sarcoid patients produced a mean (+/- SE) of 21.7 +/- 2.3 and 5.9 +/- 3.4 nmol H2O2/10(6) macrophages in the presence and absence of PMA, respectively. By contrast, AM from normals (n = 6) produced 9.8 +/- 1.7 and 1.6 +/- 0.7 nmol H2O2/10(6) macrophages with and without PMA, respectively. Macrophage activation, as monitored by H2O2 production, did not correlate with the angiotensin-converting enzyme levels, the result of gallium-67 scans, or the percent of lymphocytes in the bronchoalveolar lavage. To determine whether AM from normals could be stimulated to increase their H2O2 production to the level seen in patients with sarcoid, we measured H2O2 released by adherent AM after incubation in each of four potential activating agents: recombinant interferons alpha A, beta, gamma (rIFN alpha A, rIFN beta, and rIFN gamma, respectively), and 1,25-dihydroxyvitamin D3. H2O2 release in the range seen in sarcoid patients could be induced in PMA-triggered AM from normals by rIFN gamma in a time- (t1/2 approximately 1 d) and dose-dependent fashion (threefold increase, EC50 5 antiviral U/ml) and by rIFN alpha A and rIFN beta at higher concentrations, but not by 1,25-dihydroxyvitamin D3.

Calcitriol↗
PubMed2004

Adrenomedullin is both proinflammatory and antiinflammatory: its effects on gene expression and secretion of cytokines and macrophage migration inhibitory factor in NR8383 macrophage cell line.

Adrenomedullin (ADM) is a potent vasorelaxant peptide that plays important roles in cardiovascular homeostasis and inflammatory response. ADM derived from macrophages is one of the major sources of ADM that is produced in the inflammatory process. To assess the functions of ADM in inflammation, we studied the temporal changes in ADM production and its effect on secretion of macrophage migration inhibitory factor (MIF) and cytokine response of NR8383 rat macrophages activated by lipopolysaccharide (LPS). NR8383 cells were stimulated by LPS in the absence and presence of exogenous ADM, and the concentrations of ADM, MIF, and proinflammatory cytokines (IL-6, TNF-alpha, and IL-1beta) in the culture media and gene expressions of the cells were measured. We confirmed that the secretion and mRNA expression of ADM in the macrophages were markedly increased by LPS. ADM increased initial secretion of MIF and IL-1beta from both nonstimulated and LPS-stimulated cells, and it also increased basal and LPS-induced IL-6 secretion of the cells by 2- to 15-fold. However, it reduced secretion of TNF-alpha from LPS-stimulated cells by 34-56%. Our results suggest that ADM modulates MIF secretion and cytokine production and plays important roles in both the initiation and propagation of the inflammatory response.

Adrenomedullin↗
PubMed2004

Morphologic characteristics of pulmonary macrophages in cetaceans: particular reference to pulmonary intravascular macrophages as a newly identified type.

We examined the morphologic characteristics of pulmonary macrophages in 42 specimens of Odontoceti (Globicephala macrorhynchus, Grampus griseus, Tursiops truncatus, Stenella attenuata, Stenella coeruleoalba, Berardius bairdii), using light and electron microscopes as well as immunohistochemistry with SRA-E5. SRA-E5-positive alveolar macrophages and pulmonary interstitial macrophages contained graphitic soots, indicating the clearance of airborne, aspirated foreign bodies. Pulmonary intravascular macrophages (PIMs), positive with SRA-E5, were present within pulmonary capillaries, attaching to applied endothelial cells by cell junctions. They showed cytoplasmic tubular structures of micropinocytosis vermiformis and erythrophagocytosis, indicating their contributory role in the clearance of blood-borne particles. The uptake of pathogens by PIMs may be associated with the inducement of acute lung injury, especially bacterial infectious pneumonia. This study revealed for the first time the presence of PIMs in cetaceans.

Animals↗
PubMedDate not supplied

Morphometric comparisons of rat alveolar macrophages, pulmonary interstitial macrophages, and blood monocytes.

Pulmonary interstitial macrophages (IM) account for a substantial fraction of the total pulmonary macrophage (PM) population in the mammalian lung, with the remaining balance of extravascular mononuclear phagocytes being mainly alveolar macrophages (AM). Unlike the AM that can be harvested readily by bronchoalveolar lavage, the lung's IM subpopulation of PM has been characterized less well, primarily because of its relative inaccessibility. Recently we developed a method to isolate viable IM from rat lungs using an Fc gamma receptor affinity technique in conjunction with multiparameter flow cytometry. Using this approach, we undertook the present investigation to characterize quantitatively the structural features of the IM and to compare the morphologic attributes of this subpopulation of PM to those of flow cytometrically sorted AM and blood monocytes (BM). Measured or calculated parameters for each population included mean cellular equivalent circular diameter, cell area and volume, and nuclear, mitochondrial, cytoplasmic, and lysosomal volume densities in each cell type. Lysosomal volume densities were subcategorized further into primary lysosomes, small secondary lysosomes, large secondary lysosomes, lipid droplets, and vacuoles. Additionally, the shape, form, and surface irregularity of the cells and various subcellular components were determined. Comparisons of the size and other structural features of the AM, IM, and BM have indicated that (1) the morphologic phenotypes of these three populations of mononuclear phagocytes distinctly differ from one another, (2) the IM and BM are morphologically and morphometrically more akin to one another than they are to AM, and (3) the IM are more similar to the AM than are the BM. These findings suggest that the IM may represent a transitional stage of maturation between BM and AM. Our findings, however, do not rule out the possibility that at least some of the lung's IM are a discrete, BM-independent population of macrophages.

Animals↗
PubMed1991

Chemotactic peptides but not macrophage colony stimulating factor effect the synthesis of inositol lipids in macrophages.

Normal bone marrow derived macrophages display a wide variety of biological responses to a number of distinct agonists, for example, Macrophage Colony Stimulating Factor (M-CSF) and chemotactic peptides (such as FMLP). FMLP stimulates reactive oxygen intermediate production in these cells, whilst M-CSF stimulates DNA synthesis. We have compared the effects of these two agents on the production of novel inositol lipids in macrophages. Evidence is presented that FMLP, but not M-CSF elevate the levels of a lipid putatively identified as phosphatidylinositol-3,4-bisphosphate. The implications of this observation on proposed role of novel inositol lipids in macrophage proliferation are discussed.

Animals↗
PubMed2005

Nonobese diabetic mouse congenic analysis reveals chromosome 11 locus contributing to diabetes susceptibility, macrophage STAT5 dysfunction, and granulocyte-macrophage colony-stimulating factor overproduction.

Unstimulated monocytes of at-risk/type 1 diabetic humans and macrophages of the NOD mouse have markedly elevated autocrine GM-CSF production and persistent STAT5 phosphorylation. We analyzed the relationship between GM-CSF production and persistent STAT5 phosphorylation in NOD macrophages using reciprocal congenic mouse strains containing either diabetes-susceptible NOD (B6.NODC11), or diabetes-resistant C57L (NOD.LC11) loci on chromosome 11. These intervals contain the gene for GM-CSF (Csf2; 53.8 Mb) and those for STAT3, STAT5A, and STAT5B (Stat3, Stat5a, and Stat5b; 100.4-100.6 Mb). High GM-CSF production and persistent STAT5 phosphorylation in unactivated NOD macrophages can be linked to a region (44.9-55.7 Mb) containing the Csf2 gene, but not the Stat3/5a/5b genes. This locus, provisionally called Idd4.3, is upstream of the previously described Idd4.1 and Idd4.2 loci. Idd4.3 encodes an abundance of cytokine genes that use STAT5 in their macrophage activation signaling and contributes approximately 50% of the NOD.LC11 resistance to diabetes.

Animals↗
PubMed1998

Granulocyte macrophage-colony stimulating factor stimulates secretion of chemoattractive cytokines by peritoneal macrophages of CAPD patients.

The recruitment of immunocompetent cells to the site of inflammation represents an essential part of the host defense during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. Recently, it was shown that intraperitoneal application of granulocyte macrophage-colony stimulating factor (GM-CSF) leads to a marked transient recruitment of macrophages, paralleled by an increase in monocyte chemoattractant protein (MCP)-1. We, therefore, tested the in vitro effect of GM-CSF on the release of the chemotaxins interleukin (IL)-8 and MCP-1 by human peritoneal macrophages. Cells were stimulated with recombinant GM-CSF for 4, 12, and 20 hours in concentrations ranging from 0.1 to 100 pg/mL. Cells stimulated with lipopolysaccharide (LPS) or unstimulated cells served as control. Recombinant GM-CSF at concentrations found during CAPD peritonitis in vivo significantly increased the release of IL-8 and MCP-1 in a time- and dose-dependent manner. The maximum effect of IL-8 was observed directly after cell isolation, and decreased after a culture period of 10 days. Thus, our results indicate that peritoneal macrophages are the potential source of chemokines released upon GM-CSF stimulation.

Cells, Cultured↗
PubMed2001

Effects of pulse methylprednisolone on macrophage chemotactic protein-1 and macrophage inflammatory protein-1alpha in rheumatoid synovium.

OBJECTIVE: To determine the effect of pulse methyprednisolone (PMP; 1000 mg) on the expression of monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha in rheumatoid synovial membrane. METHODS: Seven patients with rheumatoid arthritis (RA) were studied. Arthroscopically-directed synovial biopsies were taken before and 24 hours after treatment with intravenous PMP. Synovial membranes were stained by immunohistochemical techniques with monoclonal antibodies against MCP-1, MIP-1alpha and CD68 (a macrophage marker). Quantitation of staining was performed by computer-assisted color video image analysis. RESULTS: PMP therapy was associated with a rapid (within 24 hours) and substantial decrease in the expression of MCP-1 and MIP-1alpha expression by a mean of 55% (p = 0.05) and 45% (p = 0.03), respectively, with no effect on CD68 expression in the synovial lining layer. There was no significant change in MCP-1, MIP-1alpha or CD68 expression in the synovial sublining. CONCLUSION: PMP therapy rapidly reduces MCP-1 and MIP-1alpha levels in the synovial lining layer without a fall in macrophage numbers. It thus appears that the initial effect of PMP is that of reducing macrophage activation.

Aged↗
PubMed1992

Functional characterization of mouse granulocytes and macrophages produced in vitro from bone marrow progenitors stimulated with interleukin 3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF).

Bone marrow from C3H/ouj mice was depleted to < 1% of CD11b+ granulocytes and macrophages using paramagnetic beads coated with sheep anti-rat antibodies. CD11b- cells, enriched three- to fourfold in colony-forming cells, were stimulated in liquid culture with interleukin 3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Cultures stimulated with IL-3 or GM-CSF increased cell numbers fourfold at 7 days, with the CD11b+ population increasing to 63% +/- 9% (n = 5) with IL-3 or 96% +/- 1% (n = 4) cells with GM-CSF. Functional responsiveness of the granulocytes and macrophages was assessed by flow cytometry in an oxidative burst assay using dichlorofluorescein (DCF) and a quantitative phagocytosis assay using opsonized fluorescent beads. Granulocytes and macrophages, identified by light scatter characteristics and allophycocyanine staining of CD11b, were assayed simultaneously with granulocytes from fresh mouse bone marrow and peripheral blood. GM-CSF-generated CD11b+ cells had higher oxidative responses than similar populations produced in response to IL-3. The oxidative burst of these in vitro generated CD11b+ populations was similar to the equivalent fresh bone marrow population. Oxidative burst responses of peripheral blood phagocytic cells could not be adequately measured in this system. Peripheral blood CD11b+ cells were the most phagocytic, followed by GM-CSF-stimulated CD11b+ cells; IL-3-stimulated and bone marrow CD11b+ cells were the least phagocytic. These data demonstrate that functional granulocytes can be produced in vitro using growth factors and that GM-CSF produces a more responsive cell than IL-3.

Animals↗
PubMed2004

[the effect of colonystimulating macrophage factor on activity of the nuclear organisers in central macrophages of the cultures of the bone marrow erythroblastic islands].

Erythroblastic islands of the bone marrow are morpho-functional units of erythropoiesis. The functional state of erythroblastic islands' cells of the bone marrow was for the first time defined by estimation of activity of the nuclear organisers of the central macrophages in the erythroblastic islands cultivated for 24 hrs in presence of various doses of the colony-stimulating macrophage factor. The findings indicate that increased doses of the colonystimulating macrophage factor was accompanied by a respective enhancement of the activity of nucleolar organisers in central macrophages of erythroblastic islands.

Animals↗