Different Subsets Of Macrophages Research Articles

Myeloid cells in atherosclerosis: a delicate balance of anti-inflammatory and proinflammatory mechanisms.

Atherosclerosis is chronic disease, whose progression is orchestrated by the balance between proinflammatory and anti-inflammatory mechanisms. Various myeloid cells, including monocytes, macrophages, dendritic cells and neutrophils can be found in normal and atherosclerotic aortas, in which they regulate inflammation and progression of atherosclerosis. The lineage relationship between blood monocyte subsets and the various phenotypes and functions of myeloid cells in diseased aortas is under active investigation. Various subsets of myeloid cells play diverse roles in atherosclerosis. This review discusses new findings in phenotypic and functional characterization of different subsets of macrophages, in part determined by the transcription factors IRF5 and Trib1, and dendritic cells, characterized by the transcription factor Zbtb46, in atherosclerosis. Improved understanding proinflammatory and anti-inflammatory mechanisms of macrophages and dendritic cell functions is needed for better preventive and therapeutic measures in atherosclerosis.

Tumour-infiltrating macrophages and clinical outcome in breast cancer

BackgroundMacrophages constitute a major component of the leucocytic infiltrate of tumours. Human studies show an association between tumour-associated macrophages and tumours with poor prognostic features. In breast cancer, the presence...

Regulatory Mechanisms for Adipose Tissue M1 and M2 Macrophages in Diet-Induced Obese Mice

OBJECTIVETo characterize the phenotypic changes of adipose tissue macrophages (ATMs) under different conditions of insulin sensitivity.RESEARCH DESIGN AND METHODSThe number and the expressions of marker genes for M1 and M2 macrophages from mouse epididymal fat tissue were analyzed using flow cytometry after the mice had been subjected to a high-fat diet (HFD) and pioglitazone treatment.RESULTSMost of the CD11c-positive M1 macrophages and the CD206-positive M2 macrophages in the epididymal fat tissue were clearly separated using flow cytometry. The M1 and M2 macrophages exhibited completely different gene expression patterns. Not only the numbers of M1 ATMs and the expression of M1 marker genes, such as tumor necrosis factor-α and monocyte chemoattractant protein-1, but also the M1-to-M2 ratio were increased by an HFD and decreased by subsequent pioglitazone treatment, suggesting the correlation with whole-body insulin sensitivity. We also found that the increased number of M2 ATMs after an HFD was associated with the upregulated expression of interleukin (IL)-10, an anti-inflammatory Th2 cytokine, in the adipocyte fraction as well as in adipose tissue. The systemic overexpression of IL-10 by an adenovirus vector increased the expression of M2 markers in adipose tissue.CONCLUSIONSM1 and M2 ATMs constitute different subsets of macrophages. Insulin resistance is associated with both the number of M1 macrophages and the M1-to-M2 ratio. The increased expression of IL-10 after an HFD might be involved in the increased recruitment of M2 macrophages.

Monocyte-derived dendritic cells

It has been recently demonstrated that, in addition to function as macrophage precursors, monocytes have the capacity to differentiate into dendritic cells (DCs), and therefore they play an essential role in both the innate and adaptive immunity. Monocytes display a remarkable functional diversity, allowing them to perform multiple defense functions, from pathogen elimination by phagocytosis, to the induction of antigen-specific T cell responses. This functional potential relies essentially in their developmental plasticity, permitting monocytes to differentiate into different subsets of macrophages and DCs. Although recent data suggest that the acquisition of functional specialization by monocytes is controlled by chemotactic, activation and differentiation factors, how monocyte differentiation occurs under physiological conditions remains largely unknown.

Monocyte/macrophage differentiation in dermatomyositis and polymyositis.

Recent advances have revealed significant differences in the pathogenesis of inflammatory myopathies. To determine whether different patterns of macrophage differentiation are a useful tool to delineate the major groups of inflammatory myopathies, the muscle biopsies of 11 patients with dermatomyositis and 12 patients with polymyositis were studied using different macrophage markers. In polymyositis, the early-activation markers MRP14 and 27E10 stained the majority of macrophages, which were recognized by the pan-macrophage marker Ki-M1P and which were located primarily in the endomysium. In dermatomyositis, macrophages predominantly expressed the late-activation marker 25F9 and were found mainly in the perimysium. Thus, the location and presence of different subsets of macrophages distinguish dermatomyositis and polymyositis. The predominance of early-activated macrophages in polymyositis indicates a more acute disease process. The findings in dermatomyositis, by contrast, suggest a role of persistent monocytes/macrophages in the disease process.

Correlation of the topographical arrangement and the functional pattern of tissue-infiltrating macrophages in giant cell arteritis.

End organ ischemia, fragmentation of elastic membranes, and aneurysm formation in patients with giant cell vasculitis results from an inflammation destroying the mural layers of large and medium sized arteries. Although the inflammatory infiltrate extends through all layers of the affected blood vessel, the most pronounced changes involve the intima and the internal elastic lamina. Analysis of the functional profile of tissue infiltrating CD68+ cells demonstrates that different subsets of macrophages can be distinguished. TGFbeta1-expressing CD68+ cells coproduce IL-1beta and IL-6, are negative for inducible nitric oxide synthase (iNOS), and exhibit a strong preference for localization in the adventitia. The adventitial homing of TGFbeta1+ CD68+ cells places them in the vicinity of IFN-gamma secreting CD4+ T cells which also accumulate in the exterior layer of the artery. Conversely, iNOS expressing CD68+ cells are negative for TGFbeta and are almost exclusively found in the intimal layer of the inflamed artery. The intimal-medial junction is the preferred site for 72-kD collagenase expressing CD68+ cells. Thus, TGFbeta1-producing macrophages colocalize with activated CD4+ T cells and home to an area of inflammation which is distant from the site of tissue damage but critical in regulating cellular influx, suggesting that TGFbeta1 functions as a proinflammatory mediator in this disease. iNOS- and 72-kD collagenase-producing macrophages accumulate at the center of pathology implying a role of these products in tissue destruction. These data indicate that the microenvironment controls the topographical arrangement as well as the functional commitment of macrophages.

Characterization of the mononuclear infiltrate involved in regression of halo nevi.

Halo nevi are characterized by progressive degeneration of nevus cells surrounded by a mononuclear cell infiltrate. We studied the morphological features of the nevus cells and the composition of the mononuclear cell infiltrate in 15 cases of halo nevi using immunohistochemical techniques and a battery of antibodies to different subsets of lymphocytes and histiocytes. Regression could be divided into four more or less identifiable stages, associated with different subsets of lymphocytes and monocyte-macrophage lineage cells. Stage I (preregression): nests of unremarkable nevus cells were surrounded by a moderate number of T lymphocytes (relatively small percentage of helper inducer T cells), occasional B cells and macrophages. Stage II (early regression): large number of T lymphocytes and FXIIIa-positive cells were in close contact with nevus cell clusters which showed ragged edges. Lysozyme-positive cells and epidermal Langerhans cells were mildly increased. Stage III (late regression): single nevomelanocytes showing mild atypia were present. Numerous T lymphocytes and macrophages positive for lysozyme, KP1 and/or FXIIIa were interspersed between the nevus cells. Increased numbers of epidermal Langerhans cells were present. Stage IV (complete regression): no nevus cells were observed and moderate numbers of T lymphocytes only remained. These results suggest that T cells, especially T-suppressor cells, and different subsets of macrophages participate in the regression of the nevi.

Macrophage subsets in different types of urticaria

Biopsy specimens from lesional and uninvolved skin of nine patients with delayed pressure urticaria, three patients with acute urticaria, six patients with chronic recurrent urticaria, and four patients with urticaria pigmentosa were analyzed by routine histology and by immunochemistry for their reactivity with monoclonal antibodies to three different subsets of macrophages. Skin from 12 healthy volunteers served as control. Uninvolved skin of patients did not differ from that of healthy volunteers. An antibody against activated macrophages (27E10) was reactive to a marked extent with macrophages in wheals of pressure urticaria, more variably in acute and chronic urticaria, and practically not at all in urticaria pigmentosa. Antibodies with specificities for macrophages in healing (RM3/1) and normal (25F9) tissue reacted more markedly in all but pressure urticaria lesions, compared with normal skin. These findings indicate an active involvement of inflammatory macrophages in whealing reactions while these cells play apparently no role in cutaneous mast cell proliferation (urticaria pigmentosa).

Heterogeneity of Macrophages in the Rat Evidenced by Variability in Determinants: Two New Anti-Rat Macrophage Antibodies Against a Heterodimer of 160 and 95 kd (CD11/CD18)

A set of three monoclonal antibodies (MoAbs), ED1, ED2, and ED3, has been shown to recognize in situ different subsets of macrophages in the rat. This macrophage diversity can be correlated with differences in stage of differentiation of cells belonging to one lineage. The present study quantifies this antigen distribution in the macrophage fractions of several lymphoid organs provided by Percoll centrifugation. Four new MoAbs (ED4, ED7, ED8, and ED9) raised against macrophages are included in this study. The tissue distribution of each of the four new MoAbs is determined by immuno- and enzyme-histochemistry on cryostat sections. The MoAbs recognize distinct subpopulations of macrophages. The new MoAbs ED4, ED7, ED8, and ED9 recognize granulocytes and other unrelated cell types, as well as cells of the mononuclear phagocyte system. ED7 and ED8 recognize a surface heterodimer of Mr 160,000 and 95,000.

In vitro induction of proliferation and differentiation of uncommitted spleen cells by epidermal cell-derived cytokines.

In this study of the hematopoietic functions of the cytokines released by the epidermal cells, we examined the effects of culture supernatants of epidermal cells and dermal cells from new born mice on uncommitted spleen cells. The epidermal cell culture supernatants (ECCS) stimulated the proliferation of nylon wool-passed I-A-spleen mononuclear cells (SC) much more vigorously than did the dermal cell culture supernatants (DCCS). The main responding cells were I-A-Thy-1-Lyt-1-Lyt-2-cells. Giemsa staining of cytocentrifuge preparations disclosed that SC cultured with ECCS or DCCS were composed of about 50% lymphoid cells, 30-40% granulocytes, 10% macrophages, and a few mast cells and megakaryocytes. Immunoperoxidase staining of the cytocentrifuge preparations showed that SC cultured with ECCS consisted of less than 10% I-A-, about 40% Thy-1+, 10-20% Lyt-1+, less than 6% Lyt-2+, 30-40% Mac-1+, 10-30% Mac-2+, 40-55% Mac-3+, and 10-20% Asialo-GM1+ cells. A double immunofluorescence study showed that 11% of Mac-1+ cells, 34% of Mac-2+ cells and 14% of Mac-3+ cells were I-A+, whereas all the I-A+ cells were either Mac-1+, Mac-2+, or Mac-3+, and that the percentage of Thy-1+ Asialo-GM1+ was less than 5%. In a panel of 3 available purified cytokines known to be secreted by keratinocytes which were used as a positive control, a similar stimulatory effect was recognized with GM-CSF and IL-3 but no such effect was found with recombinant IL-1. These data suggest that ECCS can stimulate the development of uncommitted SC into lymphocytes, different subsets of macrophages probably including Langerhans cells, granulocytes, mast cells and megakaryocytes. They constitute direct and convincing evidence indicating the combined effect of various cytokines released by epidermal cells on the proliferation and maturation of hematopoietic precursor cells into different immunocompetent cells in the skin.

Homogeneous populations of macrophages from histiocytic lymphoma patients as a source for macrophage subpopulations which differ in immunoregulatory properties.

The existence of subpopulations of macrophages which express a variety of regulatory activities of other branches of the immune system is suggested in a comparative study of a human macrophage long term culture ZI and a macrophage cell line DAB-1. Both cell cultures were derived from pleural effusions of patients with diffuse histiocytic lymphoma. DAB-1 cells were found to secrete factors which strongly suppress the response of normal T and B lymphocytes to the mitogens PHA, Con-A and pokeweed mitogen (PWM) (by 96-98%) and to stimulate the cytotoxic activity of NK cells. ZI cells secrete factors which have a mild inhibitory effect on the response of lymphocytes to the T-cell mitogens PHA and Con-A and a stimulatory effect on the response to PWM, whereas very little effect could be detected on the activity of NK cells. While DAB-1 cells form large clusters during growth in culture, and are capable of inducing the formation of lymphocyte rosettes around the tumor cells, ZI cells grow as a homogeneous monolayer and could not be shown to form such rosettes. The differences in the behavior of the two cell populations suggest that the malignant transformation may have affected different subsets of macrophages in each case. Cells from histiocytic lymphoma patients may therefore be a source for homogeneous subpopulations of macrophages and their isolation and propagation in culture is one approach by which such subsets can be defined characterized and classified. The biological characterization of macrophage subsets may also be of clinical importance since a transformed subset with broad suppressory activities may lead to a violet and rapidly deteriorating course of disease, as was in the case of the patient from whom the DAB-1 cell line was derived.