摘要:

AbstractIn murine ontogeny, macrophage precursor cells develop in the yolk sac and fetal liver. Primitive macrophages also appear in the yolk sac, migrate to various tissues, and differentiate into several fetal macrophage populations. Because the development of the monocytic cell lineage is incomplete in the early stage of fetal hematopoiesis, primitive/fetal macrophages are considered to originate from granulocyte‐macrophage colony‐forming cells or earlier macrophage precursors, bypassing the early monocytic cell series. In adult mice rendered severely monocytopenic by administration of strontium‐89, resident macrophages are maintained by self‐renewal. In contrast, administration of liposome‐encapsulated dichloromethylene diphosphonate (clodronate) results in the elimination of various tissue macrophage populations. The repopulation of affected macrophages is dependent on the increase of precursors in the liver and spleen during the period of macrophage depletion. Such precursors reconstitute heterogeneous macrophage subpopulations. In mice homozygous for the osteopetrosis (op) mutation, the absence of macrophage colony‐stimulating factor (M‐CSF) activity results in a deficiency of monocytes and monocyte‐derived macrophages. However, immature macrophages are present in various tissues. Administration of M‐CSF toop/opmice induces the increased proliferative capacity and the morphological maturation of macrophages. However, the responses of individual tissue macrophage subpopulations to M‐CSF are different. These results indicate that macrophage development, differentiation, and proliferation are regulated by the tissue microenvironment including the in situ production of macrophage growth factors in both fetal and adult life.

ISSN:0741-5400    

DOI:10.1002/jlb.59.2.133

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractThe morphological and functional characteristics of rat yolk sac endodermal cells, with particular reference to fetal macrophage (Mφ differentiation, were studied in vivo and in vitro using DA rat embryos from 8 to 16 days of gestation. At a very early stage (day 5–6) of gestation, endodermal cells are derived from proximal endoderm as an essential and multipotent organ with various primitive functions. Based on toluidine blue staining properties and ultrastructures, we demonstrated that the endodermal cell layer of 8–16‐day yolk sacs consists of two cell types, “clear” cells with clear cytoplasm (10%) and “dark” cells with dark cytoplasm (90%), and hypothesized that the endodermal cell layer is heterogeneous at both the morphological and functional levels. We produced three different monoclonal antibodies (mAbs), designated Mar 1, Mar 2, and Mar 3, that recognize rat Mφ populations. Mar 1 binds specifically to the cells constituting the mononuclear phagocyte system (MPS). Mφ Mar 3 antigen is a phagocytosis‐associated molecule, and Mar 2 antigen is a differentiation antigen of the Mφ subset. Application of these mAbs in both in vivo and in vitro studies allowed the functional capability and differentiation of fetal Mφs to be assessed. The Mar 3 antigen was expressed first on proximal endodermal cells on day 6 yolk sac and continued to be presented afterward. In vitro culture study demonstrated that the adhesive, phagocytic Mar 3+· Mar 1+Mφs differentiate from Mφ precursors in the endodermal cell layer after the first 13 days of gestation. Based on these findings, we proposed that clear cells in the endodermal cell layer are derived from precursor dark cells, detach from the layer, move to the mesenchymal stromas, and subsequently migrate to the fetal liver, loose connective tissue, and other intraembryonic tissues, and consequently they differentiate free Mar 1+Mφs during gestation (day 13–15). Thus, the Mφ differentiation and the peripherization of the Mφs could be almost fully developed during the prenatal period.

ISSN:0741-5400    

DOI:10.1002/jlb.59.2.139

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractLipopolysaccharide (LPS), a constituent of gram‐negative bacteria cell wall, plays an essential role in the pathogenesis of septic shock by generating endogenous mediators such as cytokines, nitrous oxide, superoxide anions, and lipid mediators. In vitro, LPS induces the transcription of a set of genes involved in inflammatory reactions by activating several types of transcription factors, particularly nuclear factor‐κB (NF‐κB). An analysis of NF‐κB activation using a cell‐free system demonstrated that two pathways converge to activate NF‐κB; one is staurosporine‐sensitive, the other is staurosporine‐insensitive and tyrosine kinase‐dependent. Furthermore, the latter pathway culminates in IκBaL phosphorylation at serine/threonine residues in its carboxyl‐terminal acidic region with dissociation of IκBα from NF‐κB, thereby activating NF‐κB. The requirement for the phosphorylation at this site was confirmed by the specific inhibition of NF‐κB activation in a cell‐free system by the synthetic peptide corresponding to this site. The in vivo administration of an anti‐CD18 antibody prevented elevation of plasma tumor necrosis factor (TNF) levels and acute lethality induced by injection of a low dose of LPS intoPropionibacterium acnes‐primed rabbits or by the administration of a single high dose of LPS into animals. Anti‐CD18 also prevented acute lethality induced by one of the main mediators of endotoxin shock, TNF‐α. Furthermore, an antibody to a ligand for CD18, intercellular adhesion molecule‐1, also prevented TNF‐induced shock as well as endotoxin shock in rabbits. These observations suggest that the interaction between leukoytes and endothelium through β2. integrin adhesion molecules may be of primary importance in mediating LPS signals in vivo.

ISSN:0741-5400    

DOI:10.1002/jlb.59.2.145

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractA new member of the mitogen‐activated protein kinase family, alternatively termed CSBP, p38, or RK, has been identified independently by several laboratories recently. Activation of this novel protein kinase via dual phosphorylation has been observed in different cell systems upon stimulation by a wide spectrum of stimuli, such as physicochemical stress and treatment with lipopolysaccharide or proinflammatory cytokines such as interleukin‐1 and tumor necrosis factor. Furthermore, CSAID™ cytokine biosynthesis inhibitors have now been determined to be potent and selective inhibitors of CSBP/p38/RK kinase activity. These inhibitors will help to dissect signaling pathways involved in inflammatory responses. In particular, for the first time a definitive signal transduction pathway can be prescribed to the action of lipopolysaccharide in cytokine production in macrophages.

ISSN:0741-5400    

DOI:10.1002/jlb.59.2.152

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractDendritic cells (DCs) are a distinct lineage of white cells that arise from CD34+progenitors in the bone marrow. DCs exhibit many specializations that lead to efficient antigen capture and presentation to T cells, both CD4+helpers and CD8+ killers. In several human tissues, DCs express the CD4 receptor for HIV‐1. Some early reports described the explosive infection of blood‐derived DCs by HIV‐1 and a severe compromise of their presenting function. In contrast, other studies described active HIV‐1 replication when DCs were interacting with CD4+T cells. This productive infection could begin with a low viral burden in DCs but required that the DCs retain their normal binding and stimulatory function for T cells. In this review we first summarize those features of the DC system that seem pertinent to HIV‐1 infection. Then we consider the current literature on the interaction of HIV‐1 with DCs, from several different tissues, in HIV‐1‐infected patients or following challenge with HIV‐1 in vitro. The literature leads to the hypothesis that HIV‐1 infection is a battleground in which DCs could be leading both of the armies, the aggressor that promotes HIV‐1 replication from relatively small numbers of infected cells and the defender that mediates T cell‐dependent resistance.

ISSN:0741-5400    

DOI:10.1002/jlb.59.2.158

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractCysteine‐rich intestinal protein (CRIP), a double zinc‐finger LIM protein, is expressed in great abundance in the intestine. We have found comparable levels of CRIP mRNA in peritoneal macrophages, peripheral blood mononuclear cells (PBMC), and lesser amounts in thymus and spleen. Because CRIP expression was high in immune cells, rats were challenged with lipopolysaccharide (LPS) to determine whether expression was altered during the acute‐phase immune response. Immunocytochemistry showed that, in adherent mononuclear cells, CRIP protein was localized in the cytoplasm. CRIP mRNA levels increased over time after LPS injection in peritoneal macrophages, PBMC, spleen, and intestine. No changes in CRIP mRNA level were seen in either liver or thymus. In PBMC, the level of CRIP mRNA decreased before increasing later in the acute‐phase immune response. CRIP protein was found in the plasma. Shortly after LPS administration plasma CRIP decreased, suggesting that CRIP was either passively diffused out of capillaries or was actively shunted into tissues to execute its function. Increased CRIP expression seen in response to IPS suggests that CRIP may play a role in immune cell activation or differentiation or in processes associated with cellular repair.

ISSN:0741-5400    

DOI:10.1002/jlb.59.2.172

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractQuartz was injected into a hind foot of BALB/c and DBA/2 mice and on days 40, 90, and 180 the progressive response ensuing in the draining popliteal lymph node (PLN) was investigated by histopathology and immunohistopathology. The area of silicotic nodules (ASN) was measured by morphometry, and, by this parameter, strain BALB/c proved to be a high responder to quartz, and strain DBA/2 a low responder, albeit both strains showed a similar degree of reactive lymphoid hyperplasia in the draining PLN. Both strains also showed a similar quartz content in the draining PLN but in BALB/c mice quartz particles were concentrated in the ASN, whereas in DBA/2 mice they were evenly dispersed over the PLN. Because the silicotic response of athymic BALB/c nu/nu mice was even stronger than that of euthymic BALB/c mice, T cells are not required for the development of silicotic nodules. This fits the notion that quartz is not an antigen and that high and low responder strains are MHC‐identical. Because quartz‐treated BALB/c, but not DBA/2 mice, showed a persistent expression of the macrophage differentiation markers MRP8 and MRP14, phenotypically the observed strain difference in silicotic responsiveness seems to be expressed at the level of macrophages.

ISSN:0741-5400    

DOI:10.1002/jlb.59.2.178

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractGadolinium (Gd) suppresses reticuloendothelial functions in vivo by unknown mechanisms. In vitro exposure of rat alveolar macrophages to GdCl3·6H2O caused cell death, as measured by trypan blue permeability, in both dose‐ and time‐dependent fashions. Even a 10‐min exposure to Gd caused significant cell death by 24 h. The morphology of Gd‐treated cells, pyknosis and karyorrhexis prior to loss of membrane integrity, suggested apoptosis. Upon flow cytometric examination, Gd‐treated propidium iodide‐excluding cells demonstrated light scatter changes characteristic of apoptotic cells (decreased forward and increased right angle scatter). Gel electrophoresis of DNA from Gd‐treated macrophages clearly showed the ladder pattern unique to apoptotic cells. Electron‐dense structures containing Gd were observed via electron spectroscopic imaging within phagosomes and also within nuclei (associated with condensed chromatin). Gadolinium, endocytosed by macrophages and distributed to nuclei, causes apoptosis of macrophages in vitro.

ISSN:0741-5400    

DOI:10.1002/jlb.59.2.189

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractAlthough the rat is commonly used for basic immunology and transplantation research, phenotypic and functional characterization of rat dendritic cells (DCs) lags behind similar studies in the human and mouse. Therefore, these features were examined using DCs propagated from cultures of rat bone marrow maintained in a medium supplemented with granulocyte‐monocyte colony‐stimulating factor. Analysis of cytospin preparations of cultured cells showed that DCs arise from OX7+myelomonocytic precursors. Typical mature rat DCs were morphologically similar to their mouse and human counterparts and expressed major histocompatibility complex (MHC) class II (common part determinant of Ia), OX62 (integrin molecule), OX7 (CD90), ICAM‐1 (CD54), and CTLA4 counterreceptor, but were negative for OX8 (CD8), OX19 (CD5), W3/25 (CD4), and ED2, a rat macrophage marker. Functional analysis of OX62+sorted DCs showed that they could effectively present the soluble antigen ovalbumin to naive T cells in vitro. A combination of anti‐MHC class II monoclonal antibody and CTLA4‐immunoglobulin inhibited allostimulatory ability more effectively than either reagent alone. Implications for studying the role of DCs in immune responses in the rat are discussed.

ISSN:0741-5400    

DOI:10.1002/jlb.59.2.196

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractThe combination of granulocyte‐macrophage colony stimulating factor (GM‐CSF) and interleukin‐4 (IL‐4) induces the growth of antigen‐presenting cells (APC) from adherent peripheral blood leukocytes. These cells have been characterized as dendritic cells (DC), yet many questions exist regarding their relationship to other DC populations and the nature of their progenitors. To address these issues, we utilized a combination of immunomagnetic depletion, cell sorting, and cell culture to isolate four distinct APC populations; macrophages expressing high levels of CD14 (CD14brightmacrophages), DC produced by culturing adherent cells in GM‐CSF and IL‐4 (cultured DC), and two different subsets of fresh DC that express low levels of CD14 (CD14dimDC). Each population exhibited a unique morphology and a unique profile of cell surface markers. In contrast to macrophages, all three DC populations expressed the DC marker CD83, as well as high levels of MHC molecules and the costimulatory molecules B7‐1 (CD80) and B7‐2 (CD86). In addition, all three DC populations presented soluble tetanus toxin antigen and stimulated T cell proliferation to levels far superior to that of macrophages. Blocking studies demonstrated a costimulatory role for B7‐1, B7‐2, and CD40 in antigen presentation, although B7‐2 expression was the single most important factor. To identify the progenitors of cultured DC, we sorted the adherent fraction of PBMC into discrete subpopulations prior to exposure to GM‐CSF and IL‐4. DC activity derived entirely from CD14+precursors and was equally demonstrable using either the CD14dimor CD14brightsubsets. Although these DC precursors lost expression of CD14 in culture, they maintained most of their other myeloid features. We conclude that human CD14+leukocytes acquire the phenotype and function of DC when cultured in GM‐CSF and IL‐4.

ISSN:0741-5400    

DOI:10.1002/jlb.59.2.208

出版商:Wiley    

年代:1996

数据来源: WILEY