摘要:

Subpopulations of human peripheral blood mononuclear lymphocytes, after depletion of B‐cells and monocytes (by sequential adherence to plastic and nylon wool columns) were separated by Percoll density gradient centrifugation and tested for their ability to proliferate in response to various mitogens, recall antigens, and alloantigens, and to develop cytolytic reactivity in vitro. The low‐density fraction [mostly large‐granular lymphocytes (LGL)] contained greater than 95% of the total cytotoxic activity of unfractionated nonadherent lymphocytes, against the natural killer (NK)‐susceptible K562 target cell, and against other NK‐susceptible targets, whereas the high‐density lymphocyte fraction (mostly classical T‐lymphocytes) demonstrated little or no cytolytic activity against these targets. Conversely, cytotoxic alloreactivity against the lymphoblasts of the donor used for stimulation developed only in the cultures of high density cells. Autologous cytotoxic reactivity, against autologous phytohemagglutinin (PHA)‐stimulated lymphoblasts, was not restricted to either subset but developed by both LGL as well as high‐density lymphocytes. LGL and high‐density T‐lymphocytes demonstrated significant proliferative responses to lectins [PHA, concanavalin A (Con A), pokeweed mitogen], and the responses of the LGL were similar in magnitude to those of peripheral blood mononuclear cells or of high‐density T‐cells. In contrast, only T‐lymphocytes responded to the specific recall antigen, purified protein derivative (PPD). These results indicate that LGL are capable of proliferative responses to various lectins, but have no detectable specific memory responses to a soluble antigen. In addition, a different subset of lymphoid cells was responsible for the development of NK‐like and specific alloreactivity. Therefore, NK cells and T‐cells, although sharing proliferative responses to mitogens, exhibit different function regarding cytotoxic effectors.

ISSN:0741-5400    

DOI:10.1002/jlb.35.6.537

出版商:Wiley    

年代:1984

数据来源: WILEY

摘要:

This preliminary investigation was concerned with the hypothesis that macrophages associated with tumors induced to regress temporarily by the action of cyclophosphamide (CY) have the capacity to suppress local T‐ or B lymphocyte responses which otherwise might cause permanent regression. Cultures of adherent cells, predominantly tumor‐associated macrophages (TAMs), isolated from two C57BL/6J (B6) sarcomas, MCA/76‐9 and 76‐64, after various periods of tumor growth or after CY injection (240 mg/kg) were shown to suppress or enhance the response of 106B6 normal spleen cells to stimulation by concanavalin‐A (Con A) or lipopolysaccharide (LPS). At any given time point, the extent of suppression or enhancement induced by adherent cells isolated from tumors after CY injection was similar to that induced by cells from progressing tumors and appeared to be more dependent on the time after the initial injection of tumor cells than on drug treatment per se. Thus, adherent cells suppressed Con A and LPS responses when they were isolated either from small (0.5 g) or large (>1.5 g) progressing tumors or from tumors 4–9 days after CY injection. However, during the logarithmic phase of tumor growth or within 4 days of injecting CY, adherent cells enhanced spleen cell mitogenic responses, particularly to LPS stimulation. The cultures of putative TAMs isolated at the various time points were seen to contain varying proportions of polymorphonuclear cells (PMNs), the proportions coinciding with the period of reduced spleen cell mitogenic responses. Cultures prepared from small or large progressing tumors contained about 10% or 20–30% PMNs, respectively, while those from tumors tested during the log phase contained less than 5% PMNs. Cultures from tumors removed within 4 days of injecting CY contained less than 5% PMNs while those prepared from tumors tested at later times contained as high as 25% PMNs by 9 days after CY injection. A comparison of peritoneal PMNs and macrophages from non‐tumor‐bearing mice in terms of their ability to influence mitogenesis indicated that PMNs at high ratios (1 PMN:2 spleen cells) could suppress responses directly. Lower ratios had either small suppressive effects or no effects but in no case was enhancement of responses seen. Peritoneal macrophages suppressed responses at a ratio of 1 macrophage:10 spleen cells but enhanced responses at ratios of 1 macrophage:100 or 1,000 spleen cells. The overall data indicated that the microenvironment of the tumor site may modulate the functional activity of macrophages, or their subpopulations, during their potential regulation of T‐ and B‐cell responses. In addition, the presence of PMNs in large numbers at these inflammatory sites may also contribute to the regulation of lymphocyte function.

ISSN:0741-5400    

DOI:10.1002/jlb.35.6.549

出版商:Wiley    

年代:1984

数据来源: WILEY

摘要:

This investigation was carried out to assess whether the progressive increase in the number of macrophages associated with growing tumors was the result of an influx of monocytes from the circulation as well as proliferation of macrophages in situ. Tumor‐associated macrophages (TAM) were identified in cell suspensions prepared from three C57BL/6J (B6), methylcholanthrene‐induced sarcomas, designated MCA/76‐9, 76‐64, and 77‐23, growing in normal or irradiated mice. When the sarcomas were implanted in B6 mice exposed to a sublethal dose (800 R) of whole body irradiation (WBI), tumors grew very slowly compared with control tumors. The TAM numbers were small and the percentages of macrophages were very low. The levels of TAM corresponded with the low number of circulating blood monocytes. However, compared with the number of TAM in the initial inoculum of tumor cells injected into the WBI or control mice, the TAM numbers over a period of 14 days increased several fold in WBI mice. That this increase was initially due to infiltration from the circulation was shown by injecting macrophage‐free, cultured tumor cells into WBI or control mice. Proliferation in situ was demonstrated by autoradiography experiments. When3H‐thymidine was injected 1 hr before excision of MCA/76‐9 tumors, labeled cells were seen in histological sections and in cell suspensions. The labeling indices for TAM from tumors growing in WBI or normal mice were not significantly different from tumor cell labeling indices. The overall data indicated that the progressive increase in TAM in these sarcomas was the combined result of monocyte infiltration and proliferation of macrophages in situ.

ISSN:0741-5400    

DOI:10.1002/jlb.35.6.561

出版商:Wiley    

年代:1984

数据来源: WILEY

摘要:

When exposed to zymosan or latex particles or heat‐inactivated staphylococci, freshly prepared human blood monocytes and granulocytes rapidly released a large fraction of their lysozyme content. Within 24 hours the total lysozyme activity in the monocyte suspensions tripled, while it doubled in the granulocyte suspensions, indicating synthesis of the enzyme following release. The monocytes in particular seemed to release and synthesize lysozyme without any other stimulus than contact with lymphocytes and the tube walls. Potassium caseinate in solution did not influence the lysozyme release. Myeloperoxidase and β‐glucuronidase, which in the granulocytes are kept in lysosomal fractions separate from most of the lysozyme, were neither released nor synthesized to a significant degree. Moreover, the minute amount of lactate dehydrogenase released indicated that the lysozyme release was not the result of cell lysis. Accordingly, the monocytes, which are not already stimulated by adherence to nonphagocytosable surfaces, are capable of selective enzyme release similar to that of the granulocytes.

ISSN:0741-5400    

DOI:10.1002/jlb.35.6.573

出版商:Wiley    

年代:1984

数据来源: WILEY

摘要:

While neutrophils from neonates respond less efficiently in vitro to a chemotactic stimulus than do adult cells, the in vivo recruitment of phagocytic cells to focal sites of inflammation in some situations appears to be similar in adults and neonates. To resolve this apparent discrepancy between the in vitro and in vivo observations, neonatal and adult rats were inoculated intraperitoneally with a variety of chemotactic agents. The neutrophil response was far more intense in adults than in neonates, strengthening the hypothesis that chemotaxis is less efficient in neonates than in adults. This relative deficiency may play an important role in the inability of the newborn to deal with infection effectively.

ISSN:0741-5400    

DOI:10.1002/jlb.35.6.583

出版商:Wiley    

年代:1984

数据来源: WILEY

摘要:

The in vitro culture conditions for the induction and synthesis of the mouse acute phase reactant, serum amyloid P‐component (SAP), were established using isolated hepatocytes. SAP synthesis was five to eight times greater with hepatocytes isolated from mice during the acute phase of inflammation vs. hepatocytes obtained from untreated mice. The induction of SAP synthesis in normal hepatocytes for LPS‐unresponsive mice was macrophage dependent. Activated macrophages provided the most “helper” activity for SAP production. Partially purified mouse IL 1 from the P388D1macrophage line also induced SAP synthesis. Only four IL 1 units/ml were required for optimal SAP induction. The addition of IL 1 in the presence of elicited macrophages provided an additive effect on hepatocyte SAP synthesis. The SAP‐inducing activity of IL 1 copurified with its thymocyte‐stimulating activity and was associated with a 11 to 25‐Kd MW polypeptide. Phenylglyoxal treatment of IL 1 inactivated its thymocyte stimulating activity but not its SAP inducing potential. Inhibition of m‐RNA synthesis, protein synthesis, N‐glycosylation, and protein secretion effectively prevented in vitro hepatocyte SAP production.

ISSN:0741-5400    

DOI:10.1002/jlb.35.6.587

出版商:Wiley    

年代:1984

数据来源: WILEY

摘要:

After 30‐min incubation, blood leukocytes of adult athymic BALB/c nude mice (nu/nu) have a distinctly higher methacrylate or yeast particle uptake than leukocytes of euthymic nu/ + or + / + mice. This permanent enhancement is not due to humoral factors, since the percentage of phagocytosing nu/nu leukocytes increases further in nu/ + littermate's plasma. Also, chronic infection or intraperitoneal immunization causes an additional transitory increase of the percentage of phagocytosing leukocytes and numbers of particles ingested; the phagocytic performance of leukocytes of euthymic mice is raised under these conditions by a greater factor. In fetuses enhanced phagocytosis of nu/nu mice is found only in monocytes. The bulk of ingestion of methacrylate particles is mediated by Fc receptors and significantly more receptors for IgG2B, IgG1, and IgG2Aare demonstrable on nu/nu neutrophils; ingestion of particles via these receptors is again higher in nu/nu neutrophils, whereas nu/nu monocytes display a higher uptake via Fc(lgG1) receptors.

ISSN:0741-5400    

DOI:10.1002/jlb.35.6.605

出版商:Wiley    

年代:1984

数据来源: WILEY

摘要:

Cyclic nucleotide metabolism was studied during human monocyte differentiation. Intracellular cAMP increased 17‐fold during in vitro differentiation. This increase was due to an increase in the specific activity of adenylate cyclase and a concomitant decrease in the specific activity of cyclic AMP phosphodiesterase. Monocyte adenylate cyclase activity was stimulated by guanine nucleotide, prostaglandin E1, isoproterenol, and epinephrine. Macrophage adenylate cyclase demonstrated less responsiveness to guanine nucleotide and was refractory to stimulation by prostaglandin E1, and to β‐adrenergic receptor agonists.In contrast to cAMP, total intracellular cGMP levels remained constant. Guanylate cyclase was found predominately in the cytosol of monocytes. The specific activity of soluble guanylate cyclase decreased during differentiation, while particulate activity increased more than 40‐fold. Cyclic GMP phosphodiesterase activity remained stable during monocyte differentiation.The ratio of cAMP:cGMP increased dramatically from 2:1 in monocytes to 9:1 in macrophages suggesting that cAMP may be an important mediator of differentiation, while cGMP metabolism decreases in the fully differentiated nonproliferating macrophage.

ISSN:0741-5400    

DOI:10.1002/jlb.35.6.617

出版商:Wiley    

年代:1984

数据来源: WILEY

ISSN:0741-5400    

DOI:10.1002/jlb.35.6.631

出版商:Wiley    

年代:1984

数据来源: WILEY

ISSN:0741-5400    

DOI:10.1002/jlb.35.6.633

出版商:Wiley    

年代:1984

数据来源: WILEY