摘要:

SummaryMucosal graft‐versus‐host reaction (GvHR) of the small intestine exemplifies an immunologically mediated enteropathy that is associated with expansion of mucosal mast cells (MMC). Quantitative measures of intestinal morphology, epithelial cell kinetics and mucosal immune activity were used to assess the effect of the immunosuppressive agent, cyclosporin A (CyA), in ameliorating this enteropathy and on increased activity of MMC in the jejunum. GvHR was induced in two groups of PVGU× PVGCrats by irradiation (4·50 Gy) and intravenqus injection of PVGCspleen cells (150 × 106). One group remained untreated, while a second group of eight rats was treated with a 50 mg/kg dose of CyA subcutaneously given daily for the first 3 days and then every second day, and which had commenced the day before induction of GvHR. On day 14, all animals were killed. Treatment with CyA prevented intestinal crypt hyperplasia but did not affect villus length, and normalized the crypt cell production rate (CCPR) from 38 to 15 cells/crypt/h (P<0·0001). CyA reduced the number of MMC and jejunal content of the MMC associated protease, rat mucosal mast cell protease II (RMCPII). Mean serum RMCPII concentration was reduced from 302 (s.d. = 112) in GvHR animals to 10 (s.d. = 6) ng/mL in GvHR/CyA‐treated rats (P<0·0001). We conclude that CyA ameliorates the enteropathy of GvHR and depresses the activation of MMC, as evident by the strongly depressed serum RMCPII concentration.

ISSN:0004-945X    

DOI:10.1038/icb.1989.25

出版商:Nature Publishing Group    

年代:1989

数据来源: WILEY

摘要:

SummaryThe influence of the respirable fraction of an iron ore dust on immunity has been studied. The iron ore dust enhanced the specific immune responses to both sheep erythrocytes and a bacterial lipopolysaccharide. The IgG class of antibody was enhanced significantly and its pattern of enhancement suggested that the iron ore dust was functioning as an adjuvant. In studies to test this possibility further, the pattern of antibody development over both the primary and the secondary immune response to sheep erythrocytes closely matched that of Freund's incomplete adjuvant and low levels of silica. The splenocytes, from animals that had received iron ore dust for various lengths of time, exhibited enhanced polyclonal mitogenic activity for phytohaemagglutinin,in vitro. These properties were seen when the dust had been inhaled or injected into the pleural cavity and persisted for over 1 year following the injection or inhalation of the dust. Attempts to show the induction of interleukin‐1 by the macrophages from mice implanted intraperitoneally with the iron ore dust were unsuccessful.

ISSN:0004-945X    

DOI:10.1038/icb.1989.26

出版商:Nature Publishing Group    

年代:1989

数据来源: WILEY

摘要:

SummaryEicosanoid production during phagocytosis of pyogenic bacteria by rabbit alveolar macrophages was studied as a model of early events in the pathogenesis of pneumonia. Adherent alveolar macrophages. prelabelled with [3HJ]‐arachidonic acid (AA), were incubated with live, opsonizedStaphylococcus aureusorPseudomonas aeruginosa(bacteria: macrophage ratio of 50:1) at 37°C for 90 min. Supernatant eicosanoids were extracted and separated by reverse phase high performance liquid chromatography (RP‐HPLC). While the amounts of labelled PGF2, TXB2, and PGD2produced in response to the two organisms were equal, the amount of PGF2αelicited byS. aureusamounted to three times that released during macrophage challenge withP. aeruginosa.Overall, preferential release of cyclooxygenase products occurred during phagocytosis ofS. aureus.In contrast, eicosanoids identified presumptively as oxygenated metabolites of AA predominated in cultures challenged with opsonizedP. aeruginosa.Live, non‐opsonizedP. aeruginosaelicited the same profile of eicosanoids, but in reduced amounts.Inhibitor studies indicated that these AA derivatives were not synthesized via the macrophage lipoxygenase pathway. Their production was dependent on the viability ofP. aeruginosa.Macrophages challenged with opsonized, heat‐killedP. aeruginosaresulted in production of an eicosanoid profile similar to that elicited byS. aureus.Secondary metabolism byP. aeruginosaof eicosanoids released from the macrophage did not contribute to the unique profile produced during the interaction of this organism with labeled macrophages.Our data indicate that during binding to macrophages, the primary human pathogen,P. aeruginosa, specifically modulates the profile of eicosanoids produced. This effect on inflammatory mediators may be of biological significance in the pathogenesis of pneumonia.

ISSN:0004-945X    

DOI:10.1038/icb.1989.27

出版商:Nature Publishing Group    

年代:1989

数据来源: WILEY

摘要:

SummaryFollowingGiardia lambliainfection in immune intact NMRI mice, increased numbers of IgM‐containing cells and decreased numbers of IgA containing cells were noticed in the lamina propria during the establishment (3‐5 days) and acute (9‐11 days) phases of infection. The decline in IgM‐containing cells during the clearance phase of infection (17‐21 days post‐infection) was accompanied by an increase in IgA and IgG‐containing cells. Our data suggest that the locally synthesized antibodies, especially of the IgA class, play a significant immunodulatory role in the clearance ofG. lambliainfection from the gut. Mice immunosuppressed using rabbit anti‐mouse lymphocyte serum or dexamethasone had significantly reduced numbers of IgA and IgG‐containing cells during all phases of infection and higher parasite loads in their jejunum. It appears that one of the reasons for increased severity and chronicity ofG. lambliainfection is the decrease in immunoglobulin‐containing cells in the gut.

ISSN:0004-945X    

DOI:10.1038/icb.1989.28

出版商:Nature Publishing Group    

年代:1989

数据来源: WILEY

摘要:

SummaryThree murine monoclonal antibodies (BC 1, BC2 and BC3) were developed against human milk fat globule membrane (HMFGM). By immunoperoxidase staining, it was found that the antigenic determinants had a predominant distribution in breast cancer tissue. In addition, the antibodies reacted preferentially with mucin derived from human milk rather than that derived from the breast cancer cell line ZR75; they also recognized polymorphic high molecular weight components (MW ≥ 230 000) in serum and in human milk fat globule membrane. Thus the antibodies appear to react with a component of the family of mucins found in breast cancer and human milk and it appears likely that at least part of each epitope is protein in nature. Antibodies BC1, BC2 and BC3 recognized related but not identical epitopes, and they appear to be co‐expressed on the same molecules as 3E1·2‐defined antigen (mammary serum antigen, MSA) which is also a member of the family of breast cancer‐related mucin. However, the 3E1 2 epitope is distinct and non‐cross‐reactive with those described for BC1, BC2 and BC3. The BC2 and BC3 defined epitopes were examined for their value in serum assays. Immunoassay was developed with a combination of two antibodies, using antibody BC3 for antigen capture and antibody BC2 or 3E1·2 for antigen detection and gave reasonable sensitivity (~85%) and specificity (~95%) in such serum tests for breast cancer. In a limited study, these tests appeared to complement the MSA test in the detection of breast cancer.

ISSN:0004-945X    

DOI:10.1038/icb.1989.29

出版商:Nature Publishing Group    

年代:1989

数据来源: WILEY

摘要:

SummaryA plasmin generation method to determine tissue plasminogen activator (t‐PA) activity in plasma is described, A protein solution of homogenized fibrin was used as a stimulator in the presence of plasminogen and the plasmin generated was measured by the release of para‐Nitroanilide (p‐NA) from the chromogenic substrate S‐2251. Plasmin generation by 5 iu/mL t‐PA in the presence of 1 CU/mL of plasminogen and 850μg/mL of fibrin solution reaches a peak at about 5 h incubation whilst in plasma, plasmin generation peaks after about 16 h incubation. The highest t‐PA activity in plasma was determined using an assay involving 18 h incubation. In the 21 subjects studied by this method the t‐PA activity at rest ranged from 0·34 to 0·92 iu/mL, with a mean of 0·57 ± 0·15 iu/mL of plasma whilst in the post‐occlusion state the activity ranged from 1·12 to 18·0 iu/mL, with a mean of 5·25 ± 4·49 iu/mL of plasma. We also found that subjects who developed petechiae during occlusion had significantly higher t‐PA activity both at pre‐ and post‐occlusion when compared with those who did not develop petechiae. The t‐PA activity of acid‐treated plasma stored at — 70°C showed no significant changes in activity after 12 weeks of storage when compared with the t‐PA activity of the same plasma tested prior to storage.

ISSN:0004-945X    

DOI:10.1038/icb.1989.30

出版商:Nature Publishing Group    

年代:1989

数据来源: WILEY

摘要:

SummaryThe binding of early pregnancy factor (EPF) to lymphocytes stimulates the release of soluble effector molecules. Studies in mice have shown that it is these factors rather than EPF as such which are inhibitory in the T cell‐dependent reactions, the adoptive transfer of contact sensitivity and the rosette inhibition test. Two factors have been identified: mEPF‐S1(Mr ∼15 000) is major histocompatibility complex (MHC)‐restricted while mEPF‐S2(Mr ∼55 000) is restricted to a locus (or loci) outside the MHC. In the present paper, evidence is presented which shows that EPF also induces the release of soluble mediators from human lymphocytes. With the rosette inhibition test two factors have been detected, both of similar size and genetic restriction to those described previously in the mouse. One factor, designated hEPF‐S1(Mr 14‐18 000), is human lymphocyte antigen (HLA)‐restricted and the other, hEPF‐S2(Mr 50‐60 000), appears to be restricted to a locus (or loci) outside the HLA complex.

ISSN:0004-945X    

DOI:10.1038/icb.1989.31

出版商:Nature Publishing Group    

年代:1989

数据来源: WILEY