摘要:

AbstractIt has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic‐syndrome dose range (eg. endotoxin, Bacillus Calmette Guerin,Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life‐threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radi‐oprotectant, we have demonstrated that host resistance to opportunistic infection is enhanced in these mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance to microbial invasion in glucan‐treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free‐radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested.

ISSN:0741-5400    

DOI:10.1002/jlb.42.2.95

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractThe macrophage is a source of many mediators with direct and indirect fibrogenic potential. In this study, release of macrophage‐derived fibroblast growth factor (MDGF) activity by murine peritoneal macrophages is examined with regard to its regulation by arachidonate metabolites. Upon stimulation with 10 μg/ml lipopolysaccharide (LPS), resident peritoneal macrophages from CBA/J mice released MDGF activity into media rapidly, reaching maximal levels in approximately 1 h. Lysates of these stimulated cells also revealed significantly increased cell‐associated MDGF activity, composing 45% of the total assayable activity. This activity, as assayed by radioactive thymidine incorporation by primary cultures of rat lung fibroblasts, was separable from interleukin‐1 (IL‐1) activity by reverse phase high performance liquid chromatography (HPLC). Furthermore, purified murine IL‐1 had no MDGF activity in this assay system. This stimulated MDGF release was enhanced by the cylooxygenase inhibitors indomethacin, Ibuprofen, and aspirin at micromolar concentrations, but inhibited in a dose‐dependent manner by prostaglandin E2(PGE2). On the other hand, nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor was inhibitory at 0.1 and 0.4 μM but not at 2.5 μM. Zymosan‐stimulated macrophages also markedly increased MDGF release, albeit with a different time course which was characterized by a delay of approximately 7 h before peak levels were attained. Such stimulation, which is known to cause increased lipoxygenase activity, was also inhibited by 0.5 μM NDGA. In contrast, the lipoxygenase pathway products leukotrienes B4(LTB4) and C4(LTC4) stimulated MDGF release in a dose‐dependent (10‐10‐10‐8M) manner, with LTC4being more potent on a per unit dose basis. Stimulation by LTC4was inhibited by the putative leukotriene receptor antagonist, FPL55712, while LTD4and LTE4did not stimulate MDGF release, thus suggesting the mediation of this effect by specific LTC4receptors. These data suggest also that products of the cyclooxygenase and lipoxygenase pathways are potentially important both as exogenous (ie, derived from cells other than the macrophage itself) and auto‐ or self‐regulators of macrophage MDGF release. This, in turn, implies that cyclooxygenase products are antifibrogenic and important in maintaining or returning to the quiescent or normal state, whereas the lipoxygenase products are profibrogenic and important in induction of fibrosis or wound‐healing and tissue repair. Any alteration in the balance between these two pathways may result in either a desirable or a harmful outcome.

ISSN:0741-5400    

DOI:10.1002/jlb.42.2.106

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractMononuclear phagocyte elaboration of E series prostaglandins (PGE) may be important in the regulation of inflammatory and fibrotic reactions. Mononuclear phagocytes are morphologically and functionally heterogeneous cells. To further understand the processes controlling inflammation and fibrosis, in particular that in the human lung, we characterized the ability of unfractionated and density‐fractionated human alveolar macrophages and blood monocytes to elaborate PGE. Alveolar macrophages and blood monocytes constitutively elaborated small amounts of PGE, and their elaboration of PGE was increased with lipopolysaccharide (LPS) stimulation. Monocytes elaborated more PGE than autologous alveolar macrophages. In addition, denser monocytes (specific gravity>1.055) and denser alveolar macrophages (specific gravity>1.044) elaborated more PGE than less dense monocytes and alveolar macrophages, respectively. When monocytes were incubated in vitro, their constitutive PGE elaboration decreased with time. However, in vitro incubation did not cause monocytes to lose their capacity to elaborate PGE in response to LPS. Thus, mononuclear phagocyte populations differ in their ability to elaborate PGE. These differences can be only partially attributed to differences in cell maturation.

ISSN:0741-5400    

DOI:10.1002/jlb.42.2.114

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractThe cell cycle progression and viability of stimulated and intact lymphocytes from 20 subjects with acquired immune deficiency syndrome (AIDS) was determined by flow cytometry. As compared to controls, 62% less AIDS lymphocytes, cultured for 72 hr in the presence of lectins (Con‐A, PHA, PWM), had entered the proliferative phases of the cell cycle, while the respective value for periodic‐acid (H5lO6)‐stimulated cells was 34%. The helper‐suppressor ratios and natural kill cell percentages of the unstimulated and PHA‐activated AIDS lymphocytes increased approximately 3‐fold after 72 hr in culture. The natural killer (NK) cell fraction of the PHA‐stimulated and unstimulated AIDS cultures comprised approximately 20% as compared to 10% in controls. However, no changes in the percentages of T‐lymphocytes were detected in the AIDS cell cultures. Throughout the culture period, viability of the unstimulated AIDS lymphocytes exceeded 90%, whereas in stimulated cultures it fluctuated within the 65‐90% range. It is concluded that the liability of AIDS lymphocytes to mitogens is probably a direct consequence of the human immunodeficiency virus (HIV) infection.

ISSN:0741-5400    

DOI:10.1002/jlb.42.2.122

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractIn this study we examined the effects of acute graft‐vs‐host disease (aGVHD) on the Brown Norway (BN) rat liver. When clinical signs of the disease appeared, rats were inoculated with fluorescent latex beads and 30 min later nonparenchymal cells were isolated from the liver. The cells were then analyzed via flow cytometry, histochemistry, and electron microscopy. Flow cytometry demonstrated that 58% of the cells from the 80 ml/min elutriation fraction (normally rich in Kupffer cells) of the non‐GVHD liver had high fluorescence intensity compared to 8% in rats with aGVHD. Determination of the cellular composition of the various fractions with electron microscopy confirmed flow cytometry observations in that only 9% of the 80 ml/min elutriation fraction of GVHD livers had peroxidase‐positive rough ER and the morphological appearance of macrophages as compared to 60% in the non‐GVHD liver. The low percentage of fluorescent‐positive Kupffer cells in the 80 ml/min elutriation fraction of the GVHD liver is attributed to a massive lymphocytic invasion of the liver and not necessarily to a defect in the mononuclear phagocyte system.

ISSN:0741-5400    

DOI:10.1002/jlb.42.2.128

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractIntracellular cAMP responses to forskolin (which stimulates independently of hormone receptors) and to several hormones were studied in mouse lymphoid cell lines of B‐ and T‐cell origin and in subpopulations of mouse lymphocytes. In the T‐cell lines, isoproterenol caused an increase in cAMP amounting at most to 28% of that caused by 100 μM forskolin. In contrast, in the B‐cell lines the increase ranged from 50% to over 100%. In 11 of 13 T‐cell lines, forskolin at 1 μM concentration potentiated the isoproterenol response five‐ to tenfold. Forskolin potentiation was also found in thymocytes and peripheral T‐cells but not in B‐cell lines. The relative increases in intracellular cAMP evoked by isoproterenol, prostaglandin E2(PGE2) and histamine varied markedly from cell line to cell line. For instance, three lines carrying the T‐helper cell marker L3T4 responded only to PGE2 and not to isoproterenol, whereas two cell lines carrying the Ly2 marker gave a higher response to isoproterenol than to PGE2. The results indicate that subsets of lymphocytes respond differently to various hormones and that these differences are maintained in continuous cell lines.

ISSN:0741-5400    

DOI:10.1002/jlb.42.2.144

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractThe synthesis and function of dermatan sulfate in peritoneal polymorphonuclear (PMN) leukocytes were studied. The peritoneal PMN leukocytes were obtained at 4, 8, and 16 h after guinea pigs were injected intraperitoneally with cassinate solution, and were incubated with [35S] sulfate or [3H] glucosamine on plastic. The total glycosaminoglycan synthesis and the proportion of dermatan sulfate to total glycosaminoglycans linearly increased with time. In order to clarify the function of the increased dermatan sulfate, peritoneal PMN leukocytes were cultured with [35S] sulfate on plastic or collagen gel. The total glycosaminoglycan synthesis on the collagen gel culture increased 1.5 times compared with that on the plastic culture, and especially, dermatan sulfate synthesis increased twofold. In addition, 65% of dermatan sulfate on the collagen gel culture was found in the cell and the collagenase‐soluble fractions. These results indicate that proteodermatan sulfate synthesized by PMN leukocytes interacts with collagen in vitro, and suggest that PMN leukocytes, which migrated to the inflammatory locus, lastly adhere to the injured tissue through the interaction of proteodermatan sulfate synthesized by themselves with collagen fibers exposed in the inflammatory locus.

ISSN:0741-5400    

DOI:10.1002/jlb.42.2.150

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractIn the rabbit model for spur cell anemia, animals fed a 5% cholesterol diet develop marked hypercholesterolemia and hemolytic spur cell anemia after several weeks on the diet. In vitro tests of granulocytes showed a 15% increase in cholesterol: phospholipid ratio, and decreased membrane fluidity measured with a fluorescent probe. Function tests revealed impairment of adherence, phagocytosis, and chemotaxis. Both a plasma factor and an intrinsic cellular defect appeared to contribute to the abnormal adherence. Bactericidal activity was normal. In vivo demargination in response to epinephrine was increased in animals on the diet, but exudation of granulocytes into sterile peritonitis fluid was diminished to 39.4% of control at 8 hours. Therefore, rabbits with experimental spur cell anemia have impaired in vitro and in vivo granulocyte function. The clinical significance of these findings for patients with spur cell anemia and less severe alcoholic liver disease is uncertain.

ISSN:0741-5400    

DOI:10.1002/jlb.42.2.156

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractA novel technique for the isolation and enrichment of human natural killer (NK) cells from peripheral blood mononuclear cells (MNC) is described. Negative selection of MNC with the lectin fromErythrina cristagalli(ECA), whether by panning or agglutination in solution, resulted in a population of lymphocytes (5‐20% of original MNC) highly enriched in cells exhibiting NK function. This enrichment was evident by a significant increase (range of 3‐50‐fold) in cells with large granular lymphocyte (LGL) morphology, K562 tumor‐binding cells, cytotoxic activity, and cells expressing NK phenotypic markers (Leu 11+, OKM1+). Analysis of the cytolytic specificity of the cells demonstrated that the lytic spectrum was typical of endogenous NK. The effector cells were responsive to augmentation of cytotoxic potential by lymphokines (IL‐2, IFNα, and IFNγ) and capable of antibody‐dependent cell‐mediated cytotoxicity (ADCC). ECA‐negative [ECA(‐)] cells were equivalent to NK isolated by Percoll gradient fractionation. NK heterogeneity was demonstrated by the observation of a small percentage (1‐5% of MNC) of NK in the ECA(+) population. This technique was found to be advantageous for the study of NK heterogeneity and NK biology.

ISSN:0741-5400    

DOI:10.1002/jlb.42.2.163

出版商:Wiley    

年代:1987

数据来源: WILEY

摘要:

AbstractThe influence of dynorphin A (DYN) and related opioid peptides on the tumoricidal function of activated murine peritoneal exudate macrophages (PEM) was investigated. Addition of DYN to macrophage cultures previously activated with mixed α + β‐inter‐feron (IFN‐α/β) and bacterial lipopolysaccharide (LPS) significantly enhanced their ability to lyse P815 murine mastocytoma cells in a 16 hr chromium‐release assay. The effects of DYN were dependent on prior macrophage activation. Peptide subfragments of DYN were effective in a manner similar to that of the 17‐amino‐acid parent molecule, indicating that peptide interaction with either κ or δ‐opioid receptors on the effector cell is effective in potentiating lytic function. The involvement of opiate receptors was confirmed by inhibition of the effects of DYN and leucine enkephalin by the opioid receptor antagonist naloxone. Finally, in addition to IFN‐α/β‐primed macrophages, DYN also augmented tumoricidal function in PEM primed for cytotoxicity by either γ‐interferon (IFN‐γ) or the calcium ionophore A23187, Indicating that DYN potentiates function in activated macrophages independent of the specific mode of activation.

ISSN:0741-5400    

DOI:10.1002/jlb.42.2.171

出版商:Wiley    

年代:1987

数据来源: WILEY