摘要:

AbstractPrimitive macrophages first appear in the blood islands of the mouse yolk sac on the ninth day of gestation. After the tenth day of fetal life, these cells differentiate into fetal macrophages and become mature, with the development of intracellular organelles. They appear in the mesenchymal layer and further immigrate into the extraembryonic coelom. The fetal macrophages do not show any cytochemical peroxidase or 5'‐nucleotidase activity, and they possess a marked proliferative capacity. Promonocytes or monocytes that have an incomplete ultrastructure emerge in the blood islands of the yolk sac a day after the occurrence of the fetal macrophages. These events suggest that fetal macrophages differentiate from primitive macrophages before the development of promonocytes or monocytes in the mouse yolk sac; they actively proliferate and are colonized into the embryonic tissues. These results also indicate that the ontogeny of the monocyte/macrophage is different in the early embryo compared with its later developmental stages.

ISSN:0741-5400    

DOI:10.1002/jlb.45.2.87

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

AbstractDifferent macrophage subsets can be discriminated in the well defined compartments of the mouse spleen by specialized functions and the presence of specific surface determinants. Red pulp macrophages, marginal zone macrophages, and marginal metallophilic macrophages are eliminated simultaneously within 24 hr by a single injection with liposome‐entrapped dichloromethylene diphosphonate (DMDP). After such elimination, these subsets show a striking difference in their kinetics of reappearance: Red pulp macrophages are back in normal numbers after 1 week, the marginal metallophilic macrophages take 2 weeks to regain fully their position at the border of the marginal zone and periarteriolar lymphocyte sheath, but it takes over 1 month for complete reappearance of the marginal zone macrophages. Marginal zone lymphocytes, also affected by treatment with the liposome‐entrapped drug, reappeared in the marginal zone within 2 weeks, indicating that marginal zone macrophages are not required for their localization and/or retention there. Approximately 2 weeks after treatment, all cells in the spleen have returned to normal numbers with the exception of marginal zone macrophages, which can be found only sporadically at that time. The results indicate that these macrophage subpopulations must have different precursor requirements. The differential reappearance of the macrophages creates the possibility of studying lineage analysis and will help to unravel the precise function of the marginal zone macrophages and marginal metallophilic macrophages in particular.

ISSN:0741-5400    

DOI:10.1002/jlb.45.2.97

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

AbstractWe examined the pathways involved in presentation of native histoplasmin by adherent splenocytes (as a source of accessory cells) to JC1, aHistoplasma capsulatum‐reactive murine T‐cell line that is CD4+. JC1 did not respond to accessory cells that had been fixed with paraformaldehyde and then exposed to histoplasmin but did proliferate to antigen‐pulsed cells that were subsequently fixed. Accessory cells that were coincubated with histoplasmin and sodium azide or 2‐deoxy‐D‐glucose failed to induce proliferation of JC1. Moreover, accessory cells exposed to the lysosomotropic agents, chloroquine and ammonium chloride, were unable to present antigen. Monensin also inhibited presentation of histoplasmin if added to accessory cells concomitant with antigen. In contrast, accessory cells that had been pulsed with antigen for 2 hr and then exposed to each inhibitor for 2 hr stimulated proliferation of JC1. The antigen‐presenting capacity of accessory cells that had been pulsed with histoplasmin for 2 hr was diminished considerably by subsequent treatment with phospholipase A2. Additional studies demonstrated that cerulenin, which depresses posttranslational lipid modification of proteins, abolished presentation of histoplasmin. The reactivity of JC1 was sharply reduced by anti‐L3T4 (CD4) or by anti‐l‐Abmonoclonal antibody. The results not only indicate that presentation of histoplasmin requires active metabolic events within accessory cells, they also delineate the pathways involved in handling this antigen.

ISSN:0741-5400    

DOI:10.1002/jlb.45.2.105

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

AbstractA chemotactic tetrapeptide from culture fluids ofStaphylococcus aureuswas purified to homogeneity by reverse‐phase high‐pressure liquid chromatography. The peptide comprises equimolar methionine, leucine, isoleucine, and phenylalanine. It inhibited binding of fluoresceinated fMet‐Leu‐Phe‐Lys to human monocytes, which showed that it interacted with the formyl‐methionyl peptide receptor and suggested that it was a formyl‐methionyl peptide. Based on a comparison of dose‐response curves for inhibition of fluoresceinated fMet‐Leu‐Phe‐Lys binding, the relative affinity of the peptide for the receptor was comparable to that of fMet‐Leu‐Phe‐Lys. At optimal concentrations, chemotactic efficacy (percentage of monocytes migrating to the attractant) was 53 ± 4%, in contrast to 36 ± 3% for the reference attractant fMet‐Leu‐Phe. Since approximately 60% of human monocytes have formyl‐peptide receptors, the bacterial peptide is capable of attracting all receptor‐bearing monocytes.

ISSN:0741-5400    

DOI:10.1002/jlb.45.2.114

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

AbstractIn an effort to define better the functional role of S‐adenosyl‐methionine‐mediated methylation reactions in modulating polymorphonuclear (PMN) functional responses to chemotactic stimuli, we investigated the effects of 3‐deaza‐adenosine (3‐DZA), a known inhibitor of methylation reactions in phagocytic cells, on formyl methionyl‐leucyl‐phenylalanine (FMLP)‐induced responses in human PMN leukocytes. Using the fluorescent cyanine dye 3,3'‐dipropylthiocarbocyanine (di‐S‐C3‐(5)) as an optical probe of membrane potential we observed that 3‐DZA at concentrations that inhibit FMLP‐induced O2−production does not significantly alter FMLP‐induced changes in transmembrane potential. Additional studies showed an inhibitory effect of 3‐DZA on FMLP‐induced PMN pinocytosis and to a lesser degree on FMLP‐induced degranulation. However, pretreatment of PMNs with 3‐DZA did not alter FMLP‐induced changes in Quin‐2 fluorescence, an indicator of changes in intracellular calcium levels. These findings demonstrate a dissociation between chemotactic factor‐induced cell membrane depolarization, changes in intracellular calcium, and specific neutrophil functional responses and suggest that chemotactic factor‐induced changes in transmembrane potential and intracellular calcium are independent of chemotactic factor‐induced methylation reactions. Furthermore, 3‐DZA did not alter phorbol myristate acetate induced O2−production or fluid pinocytosis indicating a stimulus specificity for the inhibitory effects of this agent on O2−production.

ISSN:0741-5400    

DOI:10.1002/jlb.45.2.121

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

AbstractWe have studied the effects of intracellular lipid storage on macrophage function. Mouse peritoneal macrophages were lipid loaded by three regimens modeling loading through the scavenger receptor [acetylated low density lipoprotein (Ac‐LDL) cells], by extracellular matrix‐bound LDL [low density lipoprotein complexed with dextran sulfate (DS‐LDL) cells], and by conditions of reduced cholesterol acceptors in the medium [low serum, oleic acid, Ac‐LDL (LS/OI) cells]. Significantly increased cholesterol levels in all three regimens were measured by cholesterol determination and Oil Red O staining of fixed cells. Upid‐laden cells were equal to control macrophages in binding and ingesting immunoglobulin‐coated sheep erythrocytes, reflecting Fc‐mediated endocytosis. The lipid‐laden cells were compared to control cells for secretory functions of macrophages that could be important in the atherosclerotic artery. They were still capable of producing all secretory products examined, but the quantities of H2O2and arachidonic acid metabolites were reduced in some cases, and fibrinolytic activity appeared to be increased. Western blot analysis showed a five‐fold increase in the release of tumor necrosis factor by DS‐LDL‐loaded cells. We suggest that the location of intracellular lipid pools as well as the type of lipids (and/or lipid complexes) ingested may determine the extent of functional changes.

ISSN:0741-5400    

DOI:10.1002/jlb.45.2.129

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

AbstractMacrophages (MØ) and MØ‐depleted (nonadherent) nonparenchymal cells (NPC) of the liver were examined for their cytotoxic potential against tumor cells, production of tumor necrosis factor (TNF), and release of prostaglandins (PG) following stimulation by lipopolysaccharide (LPS), interferon‐γ (IFNγ), and zymosan.Resident murine liver macrophages had no natural cytotoxicity for the TNF‐resistant target cell line P815. Activation of these cells was only obtained by a combination of IFNγ and LPS. Inflammatory murine macrophages were in a primed stage and could be activated by LPS alone in the absence of IFNγ. Rat resident macrophages resembled functionally the inflammatory macrophages of the mouse liver rather than the resident macrophages. They displayed natural cytotoxicity against all targets tested and were further activated by LPS in the absence of IFNγ. Similar results were obtained with respect to macrophage‐depleted nonadherent NPC: Mouse NPC had a low level of NK activity against Yac‐1 cells. Treatment with pyran copolymer resulted in a strong increase of cytotoxicity against Yac‐1; furthermore, a TNF‐dependent killing of Wehi 164 and TNF‐independent cytotoxicity against P815 cells were now acquired. In the rat NPC prepared from unstimulated animals expressed high levels of natural cytotoxicity against all targets.No major differences could be observed between inflammatory MØ and Kupffer cells of rat and mouse liver with regard to TNF production and TNF‐dependent killing of Wehi 164 tumor cells. The same was true for the spectrum of secreted prostanoids. Upon activation of all cell populations a marked shift toward the production of PGE2occurred. Experiments involving the cyclooxygenase inhibitor indomethacin showed enhanced TNF‐dependent tumor cell killing by nonactivated MØ in the absence of prostanoid production.

ISSN:0741-5400    

DOI:10.1002/jlb.45.2.139

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

AbstractEosinophils exhibit different levels of oxidative metabolism depending on their site of origin and various host factors that may influence metabolism. The present study examined the time course of eosinophil oxidative metabolism in animals undergoing chronic peritoneal stimulation. Eosinophils were purified from the peritoneal exudates of guinea pigs stimulated with weekly polymyxin B and saline peritoneal lavage.14C‐1‐ and14C‐6‐glucose oxidation and H2O2production were measured at week 0 and at various time points throughout 43 weeks of stimulation. Baseline oxidative metabolism of eosinophils was relatively high throughout the time course, but then declined sharply after 32 weeks. These “deactivated” cells that were recovered after 32 weeks also failed to respond to phorbol myristate acetate (PMA) or opsonized zymosan. Electron microscopy did not reveal significant differences between deactivated eosinophils and cells from earlier time points. These findings document the time course of eosinophil activation and deactivation in this model and suggest that metabolic heterogeneity of eosinophils can occur over time in response to a chronic stimulus.

ISSN:0741-5400    

DOI:10.1002/jlb.45.2.147

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

AbstractTumor necrosis factor alpha (TNF) induces lymphopenia, neutropenia, and biphasic neutrophilia after intravenous injection of 3,000 U TNF in Lewis rats. The mechanism of TNF‐induced lymphopenia was investigated by means of thoracic duct cannulation. Hourly measurements of lymphocyte recirculation via the thoracic duct failed to reveal any significant decrease in lymphocyte recirculation in TNF‐treated vs. control rats, suggesting that a decrease in lymphocyte recirculation through the thoracic duct is not the mechanism for TNF‐induced lymphopenia. The mechanism of TNF‐induced neutropenia was investigated by administering TNF to rats in whom a neutrophilia had been induced with Interleukin‐1 (IL‐1). In rats with neutrophilia, TNF resulted in a sharp decrease in the circulating neutrophil pool, demonstrating that TNF induces neutropenia by causing neutrophils to leave the circulating pool rather than decreasing neutrophil release from the marrow. The mechanism of neutropenia was furthermore shown to be due to the transient intravascular margination of neutrophils by administering epinephrine concomitantly with TNF. Epinephrine, which causes neutrophilia solely by demargination, abrogated the TNF‐induced neutropenia and actually resulted in a neutrophilia that was greater than the neutrophilia occurring in epinephrine alone‐treated rats, demonstrating both that TNF had already caused release of marrow neutrophils at the time of peripheral neutropenia, and that the paradoxical neutropenia was due to the transient intravascular margination of neutrophils. The known property of epinephrine to cause neutrophilia exclusively by demargination was proved by examination of the bone marrow of epinephrine‐treated rats in whom no decrease in marrow neutrophils was observed (in contrast to TNF‐ and IL‐1‐treated rats in whom neutrophilia is accompanied by a depletion of marrow neutrophils). The mechanism of TNF‐induced neutrophilia was investigated by modulating the magnitude of both the first and second peaks of neutrophilia by priming of rats with daily injections of IFNγ for 2 days prior to administration of TNF. The first peak of neutrophilia in IFNγ‐primed TNF‐treated rats was decreased in comparison to TNF alone‐treated rats because of the well‐known neutropenic and myelosuppressive effect of IFNγ, which resulted in a decrease in the number of neutrophils that could be recruited to cause neutrophilia. The second peak of neutrophilia in IFNγ‐primed TNF‐treated rats, however, was increased in relation to the magnitude of the first peak, an observation that is consistent with the known priming effect of IFNγ on macrophages and the concept that the second peak of neutrophilia is due to the release of endogenous monokines. A possible negative feedback role for TNF in contributing to the in vivo regulation of biological responsiveness to TNF itself was tested by administering TNF to C3H/HeJ mice (which are deficient in TNF production but not TNF receptors) and to congenic C3H/HeN mice (which are not deficient in TNF). TNF induced a greater neutropenia and a greater neutrophilia in C3H/HeJ than in C3H/HeN mice, suggesting that a tonic deficiency in TNF results in a hyperresponsive state that might be postulated to represent upregulation of TNF receptors. In conclusion, experimental evidence is presented consistent with the hypotheses that TNF‐induced lymphopenia and neutropenia are due to transient intravascular margination, that the second peak of TNF‐induced neutrophilia is due to the release of endogenous monokines, and that the state of neutrophil responsiveness to TNF may be regulated by TNF itself by a negative feedback mechanism.

ISSN:0741-5400    

DOI:10.1002/jlb.45.2.155

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

AbstractAntitumor substances (Fractions VI and VII) prepared from the NaOH extract of pine cone significantly stimulated the iodination (incorporation of radioactive iodine into an acid‐insoluble fraction) of human peripheral blood adherent mononuclear cells, polymorphonuclear cells (PMN), and human promyelocytic leukemic HL‐60 cells. In contrast, these fractions did not significantly increase the iodination of nonadherent mononuclear cells, red blood cells, other human leukemic cell lines (U‐937, THP‐1, K‐562), human diploid fibroblast (UT20Lu), or mouse cell lines (L‐929, J774.1). iodination of HL‐60 cells, which were induced to differentiate by treatment with either retinoic acid or tumor necrosis factor, were stimulated less than untreated cells. The stimulation of iodination of both PMN and HL‐60 cells required the continuous presence of these fractions and was almost completely abolished by the presence of myeloperoxidase inhibitors. The stimulation activity of these fractions was generally higher than that of various other immunopotentiators. Possible mechanisms of extract stimulation of myeloperoxidase‐containing cell iodination are discussed.

ISSN:0741-5400    

DOI:10.1002/jlb.45.2.168

出版商:Wiley    

年代:1989

数据来源: WILEY