摘要:

SummaryUsing a rat thymic epithelial cell line (TEC; IT‐45R1), the present study attempted to elucidate the mechanism of action of sex steroid hormones (SH) on the proliferation of TEC The findings were as follows: (a) the proliferation of TEC in response to SH was mediated through protein kinase C activity introduced as a result of interaction between SH and plasma‐borne inhibitors; (b) the strong inhibitory effect of SH on TEC proliferation might be mediated through the SH receptor pathway because the proliferative response was triggered by progesterone (P) and androgen (A), whereas the inhibitory response was triggered by P, A and oestrogen. These results clearly suggest that the control of TEC proliferation is a ‘shut‐off’ mechanism triggered by high plasma levels of SH. This further refers to the speculation that the development of the normal thymus may be due to a lack of this ‘shut‐off’ mechanism so that development occurs at the adequate plasma SH levels that are often observed before puberty. However, this development is inhibited at the high plasma SH levels after puberty and/or during pregnancy.

ISSN:0004-945X    

DOI:10.1038/icb.1994.29

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe vascular effects of Japanese encephalitis virus (JEV)‐stimulated splenic macrophage‐derived neutrophil chemotactic factor (MDF) were evaluated in mice. Intraperitoneal injection of MDF in mice resulted in a rapid increase in capillary permeability in a dose‐dependent manner as assessed by leakage of intravenously injected radiolabelled albumin ([125I]‐albumin) or Evans blue dye. Intradermal inoculation of MDF in rabbits caused [51Cr]‐labelled neutrophil emigration and accumulation into injected sites. Peak plasma leakage and neutrophil infiltration were observed at 1 h following MDF inoculation, and plasma leakage was restored by 2.5 h. The increase in capillary permeability was sensitive to pretreatment of mice with avil and ranitidine (H1 and H2 histamine receptor blockers, respectively), resulting in abrogation of the response; indomethacin, a prostaglandin synthetase inhibitor, did not have any effect.

ISSN:0004-945X    

DOI:10.1038/icb.1994.30

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe mechanisms involved in the inhibition of growth of a human B lymphoma cell line, B104, by anti‐MHC class II antibodies (Ab) were compared with those in anti‐IgM Ab‐induced B104 growth inhibition. Two anti‐MHC class II Ab, L227 and 2.06, inhibited the growth of B104 cells, although 2.06, but not L227, needed to be further cross‐linked with a goat anti‐mouse IgG Ab (GAM) to show the effect. L227 induced an increase in intracellular free Ca2+concentration ([Ca2+]i) from the intracellular pool and little or no protein tyrosine phosphorylation. phosphatidyl inositol turnover, or expression ofEgr‐1mRNA, whereas 2.06 plus GAM induced an increase in [Ca2+]ifrom both the intracellular and, in particular, the extracellular pools. The inhibition of B104 cell growth induced by anti‐MHC class II Ab was Ca2+‐independent and not inhibited by actinomycin D or cyclosporin A, and cell cycle arrest at the G2/M interphase was not observed. These features are very different from those observed in B104 cell death induced by anti‐IgM Ab. Neither DNA fragmentation nor the morphology of apoptosis was observed. These findings demonstrate that cross‐linking of MHC class II molecules transduced the negative signals through intracellular mechanisms different from those present in the cross‐linking of surface IgM.

ISSN:0004-945X    

DOI:10.1038/icb.1994.31

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryA major antigen of the leprosy bacillus,Mycobacterium leprae, is the 70 kDa heat shock protein (Hsp70), which has significant sequence homology with Hsp70 from other Mycobacterial species as well as Hsp70 from eukaryotes. A unique region of 70 amino acids at theC‐terminus of theM. lepraeHsp70 has been previously identified. This study investigated whether mice immunized with theC‐terminal fragment ofM. lepraeHsp70 recognize T cell epitopes in this species‐specific portion of the molecule. Murine lymphoproliferative responses to overlapping peptides spanning theC‐terminal 70 amino acids were restricted to mice of an H‐2bhaplotype and identified the presence of a determinant in sequence 567–591. Lymph node cells from mice immunized with this peptide recognized both theC‐terminal fragment and the whole Hsp70 molecule. Moreover, mice immunized with the same peptide responded to the whole Hsp70 molecule in a delayed‐type hypersensitivity reaction. The significance ofM. leprae‐specific T cell epitopes in the host response to Mycobacterial infection is discussed.

ISSN:0004-945X    

DOI:10.1038/icb.1994.32

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryCD59 is a membrane glycoprotein that regulates the membrane attack complex of complement and protects cells from autologous complement damage. Human polymorphonuclear leucocyte (PMN) expression of CD59 was confirmed by flow cytometry following staining with mAb 1F5, and western blotting revealed staining of a 19–23 kDa band. Warming of PMN from 4 to 37°C resulted in spontaneous CD59 upregulation. A dose‐dependent increase in expression following PMN stimulation with FMLP was observed and occurred within minutes, indicating that new protein synthesis was not required. Treatment of PMN with calcium ionophore A23187 resulted in similar increases in CD59 expression. This occurred in the presence or absence of extracellular calcium, indicating that upregulation was dependent on release of calcium from intracellular stores. Evidence for a mobilizable intracellular pool of CD59 was obtained by detection of increased binding of 1F5 following PMN permeabilization; CD59 could also be re‐expressed after stripping by phosphatidylinositol specific phospholipase C (PI‐PLC) by treatment with FMLP or A23187. There was a correlation between CD59 upregulation and lactoferrin release, suggesting that stores of CD59 may be associated with secondary granules. These studies indicate that PMN expression of CD59 is enhanced by cell activation and suggest the presence of an intracellular pool of CD59 which can be translocated to the cell membrane upon PMN stimulation.

ISSN:0004-945X    

DOI:10.1038/icb.1994.33

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummarySubstance P release by enteric nerves could be an initiating factor for mucosal mast cell (MMC) activation that is associated with weaning in the rat. Capsaicin, which depletes substance P from enteric nerves, should therefore prevent MMC degranulation. Rat pups received either capsaicin (50mg/kg) or vehicle control subcutaneous injections at 3 and 6 days of life. Capsaicin‐treated and control litters were killed at 16, 18, 20, 22, 24 and 26 days of life. MMC activation was measured by serum levels of rat mast cell protease II (RMCPII). Intestinal development was assessed by microdissection to measure villus area, crypt length and crypt cell production rate. RMCPII levels were similar in capsaicin‐treated and control rats and peaked at day 22 of life, and intestinal development was not retarded by capsaicin treatment. We conclude that substance P release is unlikely to be an initiating factor for the MMC activation that is associated with weaning.

ISSN:0004-945X    

DOI:10.1038/icb.1994.34

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThe purpose of this study was to produce antibodies which could be used to investigate the expression of murine (Mu)IFN‐α. Rabbits were immunized with a peptide, corresponding to the 15 COOH‐terminal amino acids of MuIFN‐α‐1, conjugated to keyhole limpet haemocyanin (KLH), and the resulting antipeptide antibodies were identified by indirect ELISA. Antipeptide antibodies were purified from rabbit immune sera by immunoadsorption to peptide immobilized on nitrocellulose and any remaining antibodies to KLH removed by immunoadsorption to KLH‐Sepharose. The characterization of the antipeptide antibodies by ELISA, immunoprecipitation, affinity chromatography and immuno‐fluorescence demonstrated that the antibodies recognize the peptide immunogen and the native IFN‐α molecule. Using these antibodies for immunofluorescence staining and flow cytometric analyses of stained cells, we have shown that unstimulated murine spleen cells produce IFN‐α This finding is in agreement with the recent demonstration of constitutive IFN‐α production by unstimulated human leucocytes and has important implications for the functions of interferons. The production, characterization and use of antipeptide antibodies as described herein may also have broader application for studies of the expression of other cytokines.

ISSN:0004-945X    

DOI:10.1038/icb.1994.35

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryWe investigated the relationship between the sensitivity of mouse splenocytes in immune response to nitrogen oxides and energy consumption rate of the cells. Macrophage‐like cells (Mm 1) pretreated with lL‐6 served as the source of the nitrogen oxides. The antibody production of both 2,4,6‐trinitrophenyl‐keyhole limpet haemocyanin‐primed splenocytes and B cell hybridomas was markedly reduced; about 20–40% of splenocytes and B cell hybridomas were killed by co‐culture with IL‐6‐treated Mm 1. Cell viability and antibody production were completely restored by the addition ofNG‐monomethyl L‐arginine to the culture medium. The cytotoxicity of the nitrogen oxides was correlated with the distance between effector and target cells. Under conditions of low cytotoxicity, antibody production by B cell hybridomas was suppressed by the nitrogen oxides, this suppression not being correlated with the reduction in cell growth. The sensitivity of the target cells differed in co‐cultures of antigen‐primed splenocytes and B cell hybridomas with IL‐6‐treated Mm 1. The nitric oxide‐sensitivity of the cells corresponded to their 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide reducing activity and ATP consumption rate. These findings suggest that nitrogen oxides act as regulatory molecules in immune response in three ways: cytostasis, reduction of cell growth and suppression of antibody synthesis.

ISSN:0004-945X    

DOI:10.1038/icb.1994.36

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryA neutrophil chemotactic factor (TfNCF) was isolated from the crude extract ofTritrichomonas foetusorganisms by a combination of anion‐exchange chromatography on DE52 and gel filtration on Sephacryl S200. TfNCF showed homogenicity by both PAGE and SDS‐PAGE. The molecular weight of TfNCF was estimated to be 22 and 24 kDa, by Sephacryl S200 gel chromatography and by SDS‐PAGE under reducing conditions. Immunization of TfNCF caused almost complete protection againstT. foetusinfection in mice. Western blot analysis probed with anti‐TfNCF antibody showed that the epitopes on TfNCF were not commonly shared on the other components ofT. foetusorganisms nor other helminthous parasite‐derived components. Furthermore, pre‐incubation of neutrophils with antigens of other helminthous parasites orN‐formylmethionyl‐leucyl‐phenylalanine did not affect the neutrophil chemotactic activity for TfNCF. These results suggest that TfNCF is a novel NCF consisting of unique epitopes for both antigenicity and neutrophil chemotactic activity. The role of NCF in the initiation of the immune response is discussed.

ISSN:0004-945X    

DOI:10.1038/icb.1994.37

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY

摘要:

SummaryThree hypotheses are suggested to explain the phenomenon of low responsiveness in domestic animals after injection of peptide vaccines. The first hypothesis proposes involvement of MHC haplotype and the special case in livestock breeding, where inheritance of the sire's haplotype can be closely examined by injection of antigen into a large number of paternal half‐sib progeny. The second hypothesis examines the effect of repeated antigen injections in overcoming age and MHC haplotype effects and distinguishing these effects from those caused by deficiencies in the T cell repertoire. The third hypothesis concerns non‐MHC effects that influence the expression of MHC haplotype effects and enable the host to mount an effective immune response. It is suggested that the antigen recognition signal from T cell receptor/MHC interaction is amplified to a varying extent in animal populations. Deficiency in this amplification through myeloid cell or cytokine responses may be yet another factor limiting immune responsiveness.

ISSN:0004-945X    

DOI:10.1038/icb.1994.38

出版商:Blackwell Publishing Ltd    

年代:2017

数据来源: WILEY