摘要:

AbstractA remarkable range of activities has been ascribed to the family of proteins known as transforming growth factor‐β (TGF‐β). Each plays an important role in development and homeostasis, influencing mesenchymal‐epithelial interactions, regulating cellular differentiation, and maintaining control of cell proliferation. Although in vitro comparisons of activity demonstrate a high degree of functional similarity, recent studies of mice with a targeted deletion of the TGF‐β1 gene reveal that true isoform‐specific activities do exist in vivo and that the three mammalian isoforms are not functionally redundant. This approach has defined a unique role for TGF‐β1 in the establishment and maintenance of normal immune function, shed new light on the relevance of endogenous TGF‐β1 to the normal wound healing process, and expanded the list of known mechanisms of TGF‐β1 activity to include endocrine functions. Thus, the TGF‐β1‐deficient mouse allows the definition of isoform‐specific activities, providing an invaluable window through which to view the principal functions of TGF‐β1 in vivo.

ISSN:0741-5400    

DOI:10.1002/jlb.59.6.769

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractThe recognition that apoptosis is regulated by an evolutionarily conserved set of polypeptides from the nematodeCaenorhabditis elegantto humans suggests that a conserved set of biochemical mechanism(s) may also be involved in the response. Work from a number of independent laboratories suggests that alterations in cytosolic Ca2+homeostasis represent one such candidate mechanism, and molecular targets for Ca2+are now being identified. This review will summarize what is known about the role of Ca2+in the regulation of apoptosis and discuss how Ca2+might interact with some of the other biochemical signals implicated in cell death.

ISSN:0741-5400    

DOI:10.1002/jlb.59.6.775

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractMembrane phospholipid asymmetry is an important regulator of cellular function and homeostasis. The activities of lipid transporters are contributing factors to the regulation of membrane lipid composition over the lifespan of the cell. Alterations in the activites of these proteins result in the movement of phosphatidylserine to the cell's outer leaflet. This promotes several physiologic responses including initiation of the coagulation cascade and cell recognition by the reticuloendothelial system.

ISSN:0741-5400    

DOI:10.1002/jlb.59.6.784

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractCell adhesion molecules provide the foundation for cell communication, trafficking, and immune surveillance central to host defense. These adhesion molecules which include selecting, integrins and members of the Ig superfamily, provide a recognition system between leukocytes, endothelial cells and matrix molecules. Leukocyte‐endothelial interactions initiate recruitment at sites of injury, infection and inflammation. Cell‐cell and cell‐matrix interactions also influence leukocyte phenotype and function. Dysregulation of these adhesion and signal transduction pathways can contribute to continued recruitment and persistent leukocyte activation with unresolved inflammation. Based on the pivotal role adhesive interactions play, the adhesion molecules provide potential targets for intervention. Selected synthetic fibronectin peptides, which inhibit leukocyte integrin binding and signal transductionin vitro, block recruitment and activation to limit inflammationin vivo.

ISSN:0741-5400    

DOI:10.1002/jlb.59.6.789

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractThe process of cancer metastasis consists of multiple sequential and highly selective steps. The vast majority of tumor cells that enter the circulation die rapidly and only a few survive and proliferate to form distant metastases. This survival is not random. Metastases are clonal in origin and are produced by specialized subpopulations of cells that preexist in a heterogeneous primary tumor. Metastatic cells of the murine K‐1735 melanoma survive in the circulation to produce experimental lung metasteses, whereas nonmetastatic cells do not. After incubation with different cytokines or LPS, nonmetastatic cells exhibit a high level of inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production, whereas metastatic cells do not. To provide direct evidence for the inverse correlation between the production of endogenous NO and the ability of K‐1735 cells to produce metastasis in syngeneic mice, highly metastatic clone 4 cells (C4.P), which express low levels of iNOS, were transfected with a functional iNOS (C4.L8), inactive mutated iNOS (C4.S2), or neomycin resistance (C4.Neo) genes in medium containing 3 mM NMA. C4.P, C4.Neo3, and C4.S2.3 cells were highly metastatic, whereas C4.L8.5 cells were not. Moreover, C4.L8.5 cells produced slow‐growing subcutaneous tumors in nude mice, whereas the other three cell lines produced fast‐growing tumors. In vitro studies indicated that the expression of iNOS in C4.L8.5 cells was associated with apoptosis. Multiple intravenous injections of liposomes containing a synthetic lipopeptide up‐regulated iNOS expression in murine M5076 reticulum sarcoma cells growing as hepatic metastases. The induction of iNOS was associated with the complete regression of the lesions. Collectively, these data demonstrate that the expression of iNOS in tumor cells is associated with apoptosis, suppression of tumorigenicity, abrogation of metastasis, and regression of established hepatic metastases.

ISSN:0741-5400    

DOI:10.1002/jlb.59.6.797

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractPeripheral blood monocytes are recruited to the inflamed mucosa of inflammatory bowel disease but the specific chemotactic signals responsible for their attraction are not known. Monocyte chemoattractant protein‐1 (MCP‐1) is a chemokine with potent monocyte attracting and activating properties and the aim of this study was to examine its expression and production in inflammatory bowel disease. In situ hybridisation demonstrated mRNA for MCP‐1 in macrophages, some of which had been recently recruited from the circulation as demonstrated by their co‐expression of the monocyte marker CD14, as well as in smooth muscle and endothelial cells in inflamed mucosa. Immuno‐histochemical studies showed a corresponding distribution of MCP‐1 protein production by macrophages, smooth muscle, and endothelial cells. By contrast minimal MCP‐1 mRNA expression and protein were found in histologically normal mucosa. Macrophages isolated from surgically resected inflammatory bowel disease colons and examined by Northern analysis expressed MCP‐1 mRNA significantly more frequently (15/24 vs. 0/19,P<0.0001) than macrophages from histologically normal mucosa from colon cancer resections. Blood monocytes stimulated by lipopolysaccharide and treated with hydrocortisone, 5‐aminosalicylic acid, or cyclosporin A showed reduced MCP‐1 expression and production in the presence of these agents. This study demonstrates increased expression of MCP‐1 mRNA and protein and cells of origin of MCP‐1 in inflamed intestinal mucosa. Together with the demonstrated influence of therapeutic agents on monocyte MCP‐1 production the findings suggest a role for MCP‐1 in monocyte attraction to the mucosal lesion of inflammatory bowel disease.

ISSN:0741-5400    

DOI:10.1002/jlb.59.6.804

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractIdentification and assessment of cell populations in bronchoalveolar lavage (BAL) specimens may be used to follow the course of a disease state or response to specific therapy. Beyond cellular assessment, there are indications that the presence and quantity of soluble surface antigens released from activated cells may lead to improved understanding and facilitated diagnosis of a number of disease states. This study evaluated soluble markers (sCD4 and sCD8) in BAL and serum from HIV‐infected individuals undergoing diagnostic bronchoscopy, and compared these values to flow cytometry‐quantified BAL and peripheral blood cell CD4 and CD8. Patient pulmonary diagnosis (based on cytology and microbiology) was compared with patient blood and BAL‐soluble and cell‐bound CD4 and CD8 to determine the relationship of these markers to disease states in this population. Serum sCD8 in patients with fungal infections was significantly elevated above sCD8 in patients withPneumocystis cariniior pulmonary bacterial infections,p= 0.0001. BAL sCD4/sCD8 ratio was also significantly different in patients with bacterial vs. fungal pulmonary infections,p= 0.01. These findings suggest that soluble markers, particularly elevated sCD8, may be an important indication of pulmonary disease progression in these HIV+patients with fungal infections.

ISSN:0741-5400    

DOI:10.1002/jlb.59.6.813

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractColony stimulating factor‐1 (CSF‐1) regulates the survival, proliferation, and differentiation of mononuclear phagocytes. To determine whether CSF‐1 plays a role in the perinatal development of these cells, CSF‐1 protein and mRNA expression in tissues and serum from fetal/neonatal mice and their mothers was analyzed. As fetal/neonatal age increased, CSF‐1 concentrations rose in liver, kidney, and lung, declined in brain and serum, and did not change in intestine and heart. Concurrently, fetal/neonatal CSF‐1 concentrations were higher in liver, kidney, and serum and lower in lung, brain, intestine, and heart than maternal tissue/serum concentrations, which showed no correlations with gestational or post‐partum stage. CSF‐1 mRNA was detected in all tissues examined and its expression increased in lung and heart and decreased in brain with increasing fetal/neonatal age. The developmental regulation of mouse CSF‐1 expression appears to be important for mononuclear phagocyte development during this period.

ISSN:0741-5400    

DOI:10.1002/jlb.59.6.817

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractA new enzyme‐affinity‐gold ultrastructural method makes use of the affinity of the enzyme, diamine oxidase coupled to gold, for its substrate, histamine, for localization of histamine in isolated human lung mast cells (HLMCs). The method works with routinely prepared ultrastructural samples, thereby allowing precise identification of ultrastructural structures that contain histamine. We used this method to identify the release of histamine from granule stores in anti‐immunoglobulin‐E (IgE)‐stimulated HLMCs and the replacement of histamine in secretory granules of HLMCs during recovery from anaphylactic degranulation in vitro. The findings show that electron‐dense granules in unstimulated HLMCs, maintained up to 24 h in culture, and in responding anti‐IgE‐stimulated HLMCs, over the same time period in vitro, contained histamine. Alteration of granules, resulting in decreased electron density of their contents, was associated with decreased label for histamine. Electron‐lucent intracytoplasmic degranulation chambers were devoid of histamine. Recovering HLMCs developed new granule stores of histamine by a mixture of conservation, synthetic, and endocytotic mechanisms.

ISSN:0741-5400    

DOI:10.1002/jlb.59.6.824

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractNormal human polymorphonuclear neutrophils (PMN) undergo rapid apoptosis during in vitro culture. In contrast, apoptosis is inhibited in PMN from patients with severe burns. This inhibition is not an inherent property of the cells but is caused by thermolabile factors present in the plasma. Endotoxin and the proinflammatory cytokines interleukin‐1 (IL‐1), interleukin‐6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐α) do not appear to be directly responsible. The ability of burn plasma to inhibit apoptosis was reduced by neutralizing antibodies to human granulocyte macrophage colony‐stimulating factor (GM‐CSF). GM‐CSF levels could not be detected in the burn plasma. However, the incubation of burn‐derived or normal leukocyte populations consisting primarily of PMN in burn plasma induced the production of GM‐CSF. The results suggest that activation of GM‐CSF synthesis by factor(s) in burn plasma may play a role in regulating inflammation by the inhibition of apoptosis.

ISSN:0741-5400    

DOI:10.1002/jlb.59.6.835

出版商:Wiley    

年代:1996

数据来源: WILEY