摘要:

Dimethylnitrosamine (DMN) exposure altered the cell‐mediated immune response of B6C3F1adult female mice as assessed by several immunological assays. Following 14 daily exposures (i.p.) to 1.5, 3.0, or 5.0 mg DMN/kg, mice exhibited a depression in their lymphoproliferative response to the T‐cell mitogens concanavalin A and phytohemagglutinin, and in their mixed lymphocyte response to mitomycin‐treated DBA‐2 spleen cells. The delayed hypersensitivity response (DHR) to keyhole limpet hemocyanin (KLH), as measured by vascular permeability changes, was decreased by over 50% at the 5.0‐mg/kg dose. When the DHR to KLH was measured by an influx of endogenously125l‐ iododeoxyuridine (lUdR)‐labelled monocytes, there was a 300% increase in the response of the 5.0‐mg‐DMN/kg group. Adoptive transfer studies using exogenously radiolabeled (51Cr) bone marrow cells from either vehicle‐ or DMN‐treated (5 mg/kg) donors indicated a>60% reduction in the DHR to KLH in DMN‐treated mice (5.0 mg/kg level) regardless of the donor treatment. Animals exposed to DMN exhibited a decreased susceptibility to Listeria monocytogenes. The dichotomy in the results of the KLH DHR measured by monocyte influx and the increased resistance to the bacterial challenge were interpreted to reflect an effect on bone marrow. The numbers of granulocyte/ monocyte stem cells were increased in a dose‐related fashion in bone marrow from DMN‐treated mice. The results indicate that DMN‐treatment impairs cell‐ mediated immunity while increasing the number of bone marrow cells differentiating to form granulocytes or monocytes with an apparent enhancement in functional activity.

ISSN:0741-5400    

DOI:10.1002/jlb.37.4.367

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Dimethylnitrosamine (DMN) exposure altered the activity of the macrophage and natural killer (NK) cell defense mechanisms against the B16F10melanoma In B6C3F1adult female mice as assessed by several immunologic assays. Following 14 daily exposures (i.p.) to 1.5, 3.0, or 5.0 mg DMN/kg, mice were injected (i.v.) with B16F10melanoma. The incidence and number of lung nodules, determined 18 days after challenge, were decreased in the DMN‐exposed animals. The initial observation indicated the mice exposed to 3 mg/kg DMN were afforded the greatest protection. However, when mice exposed to the highest dose of DMN were divided into subgroups of mice with or without ascites, there was a degree protection seen in the 5‐mg/kg‐treated mice without ascites that was comparable to that of the 3‐mg/kg group. The development of ascites is an overt toxic effect reflecting damage to the liver and was frequently associated with exposure to 5 mg/kg DMN. Exposure to DMN produced only slight changes in the activity of splenic NK cells as determined by the cytotoxicity of51Cr‐labelled YAC‐1 cells. The activity was significantly increased only in mice exposed to 3 mg/kg DMN and only at effectortarget (E:T) ratios of 30:1 and 10:1. Interestingly, the activity of the NK cells was significantly decreased at all E:T ratios in mice exposed to 5 mg/kg that developed ascites. The number of peritoneal exudate cells was decreased, albeit nonsignificantly, in a dose‐related fashion. The phagocytic activity, as measured by the uptake of fluorescent latex beads, was increased in a dose‐ related fashion with significance noted at the highest dose of DMN. The role of the macrophage in the increased resistance to the tumor challenge was assessed with bone marrow derived macrophages. The cytostatic activity versus B16F10tumor cells, as measured by the uptake of3H‐thymidine, was markedly increased in the bone marrow derived macrophages from DMN (5 mg/kg) mice when compared to vehicle controls. These results suggest that exposure to DMN alters bone marrow, particularly the differentiation of effector tumoricidal cells, which renders the host more resistant to metastatic tumor formation.

ISSN:0741-5400    

DOI:10.1002/jlb.37.4.383

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Five murine macrophage (MΦ)‐like cell lines were examined to determine their suitability for the characterization of MΦ interferons (IFNs). The J774A.1, RAW 309 Cr.1, and RAW 264.7 cell lines produced 30–800 international units (IU)/ 106cells when treated with 5–200 μg of bacterial lipopolysaccharide (LPS). No IFN was detected in LPS‐treated P388D1or PU5‐1.8 cell cultures. All cell lines produced IFN when inoculated with Newcastle disease virus (NDV); however, only 15 IU/106cells of acid stable IFN were produced in PU5‐1.8 cell cultures in comparison to 4.2 × 103‐1.7 × 104IU/106cells in the other cell lines. Most of the IFN was produced within 4 h in LPS‐treated cell cultures and within 12 h in NDV‐infected cell cultures. All IFNs were stable at pH 2.0 and were neutralized with antiserum against mouse L cell IFN. These cell lines appear competent for use in studying the synthesis, molecular weights, and regulatory functions of MΦ IFNs.

ISSN:0741-5400    

DOI:10.1002/jlb.37.4.395

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

The human leukemic myeloblast HL‐60 and monoblast U937 cell lines have made important contributions to the disciplines of cancer, hematology, and immunology. As sources of leukemic cells, they have been used for the study of neoplasia and therapeutics. As sources of hemic cells, they have been used for biochemical and biological analysis of regulation and differentiation in myelopoiesis. When stimulated with immunomodulatory factors, the cell lines develop properties of host‐defense effector cells. They are also a source of cytokines that affect other cell types.

ISSN:0741-5400    

DOI:10.1002/jlb.37.4.407

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Neutrophils from human neonates exhibit abnormalities of plasma membrane and cytoskeletal dependent functions such as chemotaxis, deformability, and lectin capping. The uptake of extracellular calcium by neutrophils is a key early event in neutrophil activation and in the optimal performance of these functions. We found that neonatal and control neutrophils acquire extracellular radioactive calcium comparably under most experimental conditions. No differences (P>0.05) were seen between neonatal and control neutrophils following stimulation with soluble sodium fluoride, N‐formyl‐methionyl‐L‐leucyl‐L‐ phenylalanine, dimethylsulfoxide, and opsonized zymosan particles. However, the uptake of calcium by resting (unstimulated) neutrophils was significantly less (P<0.0001) by neonatal cells. The kinetics of calcium uptake by neonatal and control neutrophils were similar both at rest and following stimulation for 15 min with sodium fluoride. Although additional studies will be necessary to completely define the ionic events involved in the chemotaxis of neonatal neutrophils, it seems unlikely that the abnormal mobility of these cells is due simply to an inability of neonatal neutrophils to acquire extracellular calcium in response to cellular stimulation.

ISSN:0741-5400    

DOI:10.1002/jlb.37.4.423

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Purified human peripheral blood polymorphonuclear neutrophils (PMN) were incubated at 37°C with the fluorescent membrane potential sensitive cyanine dye di‐O‐C(5)(3) and exposed to a number of stimulatory agents (N‐ formylmethionylleucylphenylalanine (FMLP), cytochalasin B (cyto B) + FMLP, phorbol myristate acetate (PMA). Flow cytometry was utilized to measure changes in forward light scatter (FS), orthogonal light scatter (90°‐SC), and fluorescence intensity of individual cells over time. A saturating (10−6M) dose of FMLP lead to a significant increase in the cells' FS without a change in 90°‐ SC as well as a heterogeneous loss of di‐O‐C(5)(3) fluorescence. PMA (100 ng/ ml) also caused an increase in FS but a uniform loss of dye fluorescence by all cells (apparent depolarization). Cyto B + FMLP produced an increase in FS, a marked loss of 90°‐SC, and a uniform loss of fluorescence. Secretion experiments under identical incubation conditions indicated a significantly positive relationship between loss of enzyme markers or cell granularity and orthogonal light scatter (r = 0.959, 0.998fand 0.989 for loss of 90°‐SC vs lysozyme, 0‐ glucuronidase, and granularity index, respectively). Sequential exposure of PMN to PMA and then cyto B + FMLP produced a stepwise shift in scatter parameters (increased FS then loss of 90°‐SC). Normalization of membrane potential dye fluorescence changes for the changes in light scatter did not abrogate the heterogeneous fluorescence response of cells to stimulus, indicating that stimulus‐induced scatter changes were not responsible for such fluorescence shifts. The data demonstrate that loss of 90°‐SC relates closely to secretion of primary granules while changes in FS reflect alterations in cell shape and/or surface/volume ratios that accompany cell activation. Flow cytometric light scatter measurements may yield important information on the extent of prior cell degranulation or activation.

ISSN:0741-5400    

DOI:10.1002/jlb.37.4.431

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

The in vitro effect of colloidal suspensions of alpha‐tocopherol (α‐T) on phorbol‐ myristate‐acetate (PMA)‐induced monocyte cytotoxicity and on antibody‐dependent monocyte cytotoxicity (ADCC) was studied. We observed that 1) in the presence of α‐T, the inhibition was twice as high in the PMA‐induced assay than in ADCC; 2) monocytes preincubated with α‐T were inhibitory in both assays but much less in ADCC, and 3) target erythrocytes preincubated with a‐T decreased the cytotoxicity in the PMA‐induced assay only. Since α‐T preincubated monocytes showed a decreased release of H2O2but not of O2″, we concluded that one of the mechanisms by which α‐T decreased cytotoxicity could be decreased release of H2O2. Whereas the role of H2O2was documented in the PMA‐induced cytotoxicity, in ADCC non‐oxidative injury seems more important. This is supported by 1) lesser inhibition of the assay with α‐T preincubated monocytes; 2) lack of protection with α‐T preincubated erythrocytes, and 3) mild inhibition with protease inhibitor.

ISSN:0741-5400    

DOI:10.1002/jlb.37.4.449

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Human peripheral blood monocytes were incubated with free or liposome‐ encapsulated human lymphokines containing macrophage‐activating factor (MAF) and tested for their effect on herpes simplex virus (HSV)‐infected target cells. Activated monocytes lysed allogeneic HSV type 2 (HSV‐2)‐infected whole human embryo cells and xenogeneic BALB/c mouse embryo cells (10E2) without any significant effect on uninfected cells, as measured by release of51Cr from target cells after 18 h of cocultivation. Kinetic studies revealed that lysis of virus‐infected cells occurred by 10 h following cocultivation with activated monocytes. The inability of free MAF or supernatants from MAF‐acti‐ vated monocytes to lyse HSV‐2‐infected cells suggested that direct monocyte‐ target cell contact is required for monocyte‐mediated cytotoxicity of the virus‐ infected cells. Monocytes activated with MAF suppressed the production of HSV‐2 and HSV‐1 from virus‐infected cells more than control monocytes did. In addition, monocytes treated with liposome‐encapsulated MAF selectively destroyed HSV‐2‐infected cells but left uninfected cells unharmed. The capacity of liposome‐encapsulated immunomodulators to activate human monocytes to selectively lyse HSV‐2‐infected cells has potential therapeutic benefit and should be evaluated in vivo.

ISSN:0741-5400    

DOI:10.1002/jlb.37.4.461

出版商:Wiley    

年代:1985

数据来源: WILEY

ISSN:0741-5400    

DOI:10.1002/jlb.37.4.473

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Investigators from two different laboratories have compared several variables in the short‐term macrophage‐mediated cytotoxicity assays used by each group to study the role of MulFN‐ γin macrophage activation. The findings suggest that the capacity of MulFN‐ γto activate macrophages without the need for a second triggering stimulus is related to assay conditions and, most especially, the strain of mouse used to provide the macrophages.

ISSN:0741-5400    

DOI:10.1002/jlb.37.4.475

出版商:Wiley    

年代:1985

数据来源: WILEY