摘要:

AbstractThe ability of macrophages to function in the presence of δ9‐tetrahydrocannabinol (THC), the major psychoactive component in marijuana, was evaluated. THC added to macrophage cultures prepared from human peripheral blood inhibited macrophage spreading and phagocytosis of yeast. The effects of THC were concentration dependent, with inhibitory effects observed from 10 to 1 μg ml or lower. These results suggest that macrophages are more sensitive to THC than are lymphocytes because macrophage functions were inhibited by THC at concentrations that did not affect lymphocyte function. Thus, inhibition of lymphocyte function(s) by THC could be attributed to a direct effect of the drug on macrophages which indirectly results in lowered lymphoid cell activity.

ISSN:0741-5400    

DOI:10.1002/jlb.50.5.423

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Abstract1,25‐dihydroxyvitamin D3[1,25(OH)2D] is known to stimulate maturation of the human promyelocytic line HL‐60 and murine bone marrow precursor cells along a monocyte/macrophage pathway. In this study, the steroid's effects on the PLB‐985 leukemic line were examined. We found that 1,25(OH)2D induces monocytic differentiation of PLB‐985 as manifested by morphological appearance, histochemical staining, and changes in cell surface antigen expression. Additionally, there was acquisition of functional monocyte characteristics including phagocytic activity and superoxide anion production via the respiratory burst pathway. Steady state levels of mRNA derived from the leukocyte‐specific proto‐oncogene c‐fgrwere also increased by the steroid. Thus, 1,25(OH2)D effectively differentiates PLB‐985 cells along a monocytic pathway, providing a useful model of macrophage differentiation.

ISSN:0741-5400    

DOI:10.1002/jlb.50.5.427

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractIn order to directly monitor neutrophil aggregation, we have developed a simple particle counting technique using flow cytometry. Flow times were used to determine aggregation from changes in the total number of particles per unit volume (%PAT), while fluorescent signals emitted from glutaraldehyde‐fixed neutrophils were used to measure changes in the total number of singlet neutrophils (%PAgs). Flow cytometrically‐determined %PA values were found to be virtually identical to values determined from microscopy. We show that aggregation parameters can be evaluated and compared simply from measures of changes in total particle count without a need for distinguishing singlets from murtiplets. A number of aggregation parameters are introduced and related to the initial cell concentration (No) and stir speed (shear). Aggregation of neutrophils, following stimulation with 0.5 μM FMLP (N‐formyl‐methionyl‐leucyl‐phenylalanine), showed a latent time (ti) of 4 ± 1.5 sec independent of Noor stir speed; had a forward rate of aggregation (v,) which was proportional to the initial cell concentration and the stir speed; plateaued for ≥ 60 s; and showed partial to complete reversal by 7.5 min. Above a critical stir speed, the extent and duration of aggregation varied inversely with the stir speed. The stir and Nodependence of the aggregation parameters studied suggest the existence of subpopulations of neutrophils with distinct efficiencies of aggregation.

ISSN:0741-5400    

DOI:10.1002/jlb.50.5.434

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractHuman neutrophils isolated from the blood were incubated in vitro for 30 min with 25 ng/ml of phorbol 12‐myristate 13‐acetate (PMA), a protein kinase C activator, to study its effect on the fine structure of granulocytes and on the subcellular distribution of lactoferrin (Lf). Flow cytometry analysis of the human neutrophils showed that PMA induced a decrease in size and granularity of the cells. By electron microscopy, the PMA‐treated cells showed numerous empty vesicles, smoothing of the cell surface, and a marked decrease in the compactness of the cytoplasmic ground substance. High‐resolution immunogold ultracytochemistry showed that neutrophils lost most of their content in Lf after the PMA incubation. In thin sections, the cytoplasmic compartment of PMA‐treated neutrophils contained an average of 1.03 ± 0.3 Lf‐positive vesicles per μm2, whereas control granulocytes showed an average of 5.72 ± 1.49 Lf vesicles per μm2of cytoplasm. Most of PMA‐treated neutrophils kept some Lf‐positive vesicles; a significant minority (10–15%) of the granulocytes showed cytological features of cell death. We conclude that the PMA‐induced neutrophil activation is associated with microanatomical changes that include i) exocytosis of most, but not all, of the Lf‐bearing vesicles; ii) rounding up of the cell outline; and iii) decrease in the compactness of the cytoplasmic ground substance.

ISSN:0741-5400    

DOI:10.1002/jlb.50.5.444

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractWe investigated the effects of bacterial lipopolysaccharide (LPS), immune complexes (IC), and C3b opsonized zymosan (AZ) alone and in combination with lnterferon‐γ (IFN‐γ) priming on macrophage synthesis and secretion of C1q. Our results indicated that LPS, IC, and AZ alone stimulated C1q mRNA and secretion in the absence of IFN‐γ. The increase in mRNA accumulation was detectable after 3 h, peaked at 6h and was maintained at constitutive levels for 24 h. There was a corresponding early burst of increased secretion of functional C1q after 3 to 6 h which declined rapidly after 9 to 24 h culture of LPS‐stimulated macrophages. Priming of macrophages with IFN‐γ and simultaneous triggering with LPS, IC, or AZ produced additive rather than synergistic increases in C1q mRNA accumulation. These same agents inhibited constitutive secretion of C1q in the absence of IFN‐γ priming as determined by autoradiographic analysis of metabolically radiolabeled secretory C1q. Triggering of IFN‐γ primed macrophages with LPS, IC, or AZ also markedly suppressed the increased rate of C1q secretion induced by IFN‐γ in a dose‐related fashion. A corresponding dose‐dependent increased accumulation of endogenous C1q in cell lysates was detected by Western blot analysis of macrophages which had been stimulated by LPS, IC, or AZ alone or in combination with IFN‐γ. Our findings indicate that LPS as well as FcR and C3bR triggering agents stimulate early and sustained C1q synthesis accompanied by an early and short‐lived burst of C1q secretion which rapidly diminished and results in an increased intracellular accumulation of C1q due to ongoing synthesis. IFN‐γ appeared to further amplify the same kinetics of increased C1q mRNA accumulation and decreased extracellular accumulation mediated by LPS, IC, and ZM. Our results suggest that LPS, IC, and AZ alone or in combination with IFN‐γ stimulate early C1q production to modulate macrophage effector functions followed by an inhibition of C1q secretion when the activation process has been culminated.

ISSN:0741-5400    

DOI:10.1002/jlb.50.5.453

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractAdhesion between lymphocytes and antigen‐presenting cells is necessary for the development of certain immune reactions. We have previously shown that fibronectin (FN) added to mixed lymphocyte cultures (MLC) can restore a decreased lymphocyte proliferation in immunocompromised individuals. Using highly purified cell populations from peripheral blood for depletion and adding back experiments we show here that exogenous FN enhanced proliferation only when allogeneic monocytes were co‐cultured with responder lymphocytes. Although lymphocyte proliferation in MLC was augmented by FN, there was no preferential proliferation of any particular major lymphocyte subpopulation in cultures supplemented with FN as compared to control cultures lacking its addition. Antibody against the FN receptor (FN‐R) of the β1integrin family, as well as Arg‐Gly‐Asp containing peptide, could inhibit alloantigen‐induced lymphocyte proliferation in a concentration‐dependent manner. Anti–CD3‐lnduced proliferation was inhibited by anti–FN‐R antibody but not Arg‐Gly‐Asp peptide whereas no inhibition was seen with the phytohemagglutinin (PHA)‐induced lymphocyte proliferation. This study presents further evidence that FN and its receptor (α5β1) are involved in the augmentation of T‐cell responsiveness to proliferative stimuli.

ISSN:0741-5400    

DOI:10.1002/jlb.50.5.464

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractStudies designed to identify a panel of monoclonal antibodies useful for the separation of murine eosinophil myeloid progenitors revealed that F4/80, an antigen heretofore thought to be expressed only by murine monocyte/macrophage lineage cells, was expressed by eosinophil granulocytes. Eosinophils from several strains of mice stained positively with specific antibody for the epitope. A novel pathway for myeloid differentiation is proposed in which neutrophil progenitors exit a common lineage prior to a common progenitor of monocytes and eosinophils. Moreover, the results demonstrate that binding of anti‐F4/80 can no longer be viewed as exclusive for mononuclear phagocytes.

ISSN:0741-5400    

DOI:10.1002/jlb.50.5.471

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractWe examined the mechanism by which Polyriboinosinic:Polyribocytidylic acid (Poly l:C) augments resistance of thioglycolate‐elicited inflammatory macrophages to infection with herpes simplex virus type 1 (HSV‐1). We show that Poly l:C‐induced antiviral activity is completely abrogated by antibodies to interferon‐β (IFN‐β) whereas antibodies to other interferons or to other cytokines have no effect. Furthermore, treatment of inflammatory macrophages with exogenous IFN renders them resistant to HSV‐1, whereas treatment with other cytokines does not. In addition, we demonstrate that supernatants from macrophages treated with Poly l:C contain IFN‐β but not IFN‐α. Taken together these data indicate that the antiviral effects of Poly l:C in inflammatory macrophages are mediated solely by IFN‐β, which acts in an autocrine manner to induce resistance to HSV‐1.

ISSN:0741-5400    

DOI:10.1002/jlb.50.5.479

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractThe objective of this study was to determine whether agents that either scavenge or inhibit the production of oxygen radicals can alter the adhesive interactions between leukocytes and venular endothelium elicited by ischemia‐reperfusion. Cat mesenteric and intestinal blood flows were reduced to 20% of baseline for 1 hr, followed by 1 hr of reperfusion. Sixty minutes after reperfusion, red blood cell velocity (Vr), leukocyte rolling velocity (Vw), and the number of adherent leukocytes were measured in mesenteric venules. Then, either manganese‐superoxide dismutase (Mn‐SOD), catalase, desferrioxamine, or oxypurinol was administered intravascularly. Ten minutes later, repeat measurements were obtained and compared with pretreatment values. Catalase, Mn‐SOD, and oxypurinol significantly attenuated neutrophil adherence while neither inactivated‐catalase nor desferrioxamine altered the reperfusion‐induced leukocyte adhesion. The ratio of Vw to erythrocyte velocity, an index of the fracture stress between rolling leukocytes and venular endothelium, was not altered by any of the agents studied. These results and data in the literature indicate that many of the agents that are commonly used to either scavenge or inhibit the production of oxygen radicals in postischemic tissues exert a significant inhibitory influence on leukocyte adhesion to microvascular endothelium in vivo. Our results are also consistent with the view that xanthine oxidase‐derived oxidants contribute to the leukocyte‐endothelial cell adhesive Interactions associated with reperfusion of ischemic tissues.

ISSN:0741-5400    

DOI:10.1002/jlb.50.5.488

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

AbstractHerein we demonstrate that continuous infusion of either TNF‐α or IFN‐γ (104U/day) via osmotic micropumps leads to an increased resistance of mice infected with a lethal dose (107) ofM. tuberculosisH37Rv, associated with a decreased microbial growth in all target organs. This result was reinforced by the finding that infusion of antibodies against TNF‐α or IFN‐γ greatly enhanced susceptibility of naive mice to tuberculosis. In a final set of experiments, using neutralizing antibodies, we show that IFN‐γ, not TNF‐α is involved in determining acquired resistance against murine tuberculosis, as seen by the fact that acquired immunity is resistant to anti‐TNF‐α antibodies, yet sensitive to anti‐IFN‐γ antibodies. This suggests a role for both IFN‐γ and TNF‐α in determining innate resistance whereas IFN‐γ may be the mediator of the anamnestic response.

ISSN:0741-5400    

DOI:10.1002/jlb.50.5.495

出版商:Wiley    

年代:1991

数据来源: WILEY