ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1994.tb00285.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractVCAM‐1 (vascular cell adhesion molecule‐1) is a cytokine‐in‐ducible adhesion molecule which is known to mediate adhesion of mononuclear cells to endothelial cells in vitro via binding to the integrin VLA‐4 (very late antigen‐4). To further elucidate the role and regulation of VCAM‐1 in vivo, we compared in vitro and in vivo expression of VCAM‐1 in response to cytokines and investigated immunohistochemically the expression of VCAM‐1 in three murine models of experimental inflammation. These models differed with regard to the pathogenetic mechanism and the subsequent infiltrate: allergic contact dermatitis (ACD) to DNFB as a T cell‐controlled, DTH type of inflammation, cutaneous infection with Leishmania major as a chronic granulomatous inflammation and the cauterized cornea as a model for acute inflammation. VCAM‐1 was found to be markedly enhanced on vascular endothelia in all types of inflammation and after subcutaneous administration of LPS and TNF‐a. Administration of IL‐4, however, failed to induce VCAM‐1 both in vivo and in vitro. The increased VCAM‐1 expression in the inflammatory models correlated with the appearance of infiltrating monocytes/ macrophages. A concomitant influx of CD4‐positive/CD8‐positive lymphocytes was only

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1994.tb00286.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractMacrophages play important roles in immunity and inflammation, and in allergic, granulomatous and neoplastic diseases. Here, we present the indepth results of an ongoing study of macrophage differentiation pathways in cutaneous macrophage disorders and in vitro. Up to now, a total of 40 cases of cutaneous macrophage disorders (histiocytoses and granulomas) and related diseases were examined using a panel of monoclonal and polyclonal antibodies to macrophage differentiation antigens (mAb MS‐1, mAb αCDla, mAb αCD34, mAb RM 3/1, mAb αCD11c, mAb αCD36, mAb MAC 387, mAb 27E10, polyclonal antibodies ccMRP‐8 and ‐14, mAb aCD68. mAb 25F9, mAb DRC1‐R4/23, and mAb 1F10). Of these, MS‐1 high molecular weight protein, synthesized by non‐continuous sinusoidal endothelial cells and highly dendritic perivascular macrophages in normal human organs, is the most specific macrophage differentiation marker. MS‐1 high molecular weight protein is selectively expressed by cutaneous non‐Langerhans cell histiocytoses, and proves to be a valuable diagnostic tool for these diseases. MS‐1 high molecular weight protein is not found in Langerhans cell histiocytosis cells, epithelioid cells in sarcoidosis, and palisading histio‐cytes in granuloma annulare. MS‐1+ macrophages may be found intermingled in cellular type dermatofibroma and in foreign body granulomas; they differ from MS‐1+ non‐Langerhans cell histiocytosis cells by their highly dendritic morphology, and thus rather resemble the MS‐1+ macrophages in normal skin. RM 3/1 antigen shows a similar, but broader expression pattern including non‐Langerhans cell histiocytoses, xanthel‐asmata palpebrarum, foreign body granulomas, granuloma annulare, and cellular type dermatofibroma. Moreover, xanthelasmata palpebrarum para‐digmatically represent a class of macrophage lesions with strong RM 3/1, but little MS‐1 antigen expression. In sarcoidosis, RM 3/1 + macrophages are only found at the very periphery of epithelioid cell granulomas. In contrast, 25F9 antigen is strongly and consistently expressed in epithelioid cells of sarcoidosis, and in foreign body granulomas. In cultured human monocytes/macrophages, RM 3/1 antigen is expressed early on, while MS‐1 high molecular weight protein and 25F9 antigen are late and very late macrophage differentiation antigens, respectively. Expression of RM 3/1 antigen and MS‐1 high molecular weight protein is inducible by glucocorticoid and interleukin‐4, and less so by interleukin‐13 and interlcukin‐10, and combinations thereof, while 25F9 antigen seems to be less influenced by these agents. Interferon‐y (and less so tumor necrosis factor‐ex) inhibit expression of all three antigens in cultured human monocytes/macrophages. In monocytic leukemia cell line THP‐1. RM 3/1 antigen is only induced by a combined treatment of phorbolester and glucocorticoid and peaks at 3‐7 days. In different subclones of the cell line, 25F9 antigen is either inducible by phorbolester alone or by combined treatment with glucocorticoid or it is constitutively expressed and hardly modulated. In contrast, MS‐1 high molecular weight protein cannot be induced in THP‐1 cells by the agents tested. Inhibition of MS‐1 high molecular weight protein, and RM 3/1 and 25F9 antigens by interferon‐y suggests that macrophages characterized by these phenotypic traits must by counted among the alternatively activated macrophage populations. As a result of our study, alternative macrophage activation should be viewed as a multifacetted process resulting in various, partially overlapping, partia

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1994.tb00287.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe epicutaneous application of haptens results in a functional activation of the antigen‐presenting Langerhans cells (LCs) which is necessary for the induction of contact sensitivity. In this ultrastructural study, We investigated the effects of the immune response on these cellular properties of the LCs by using 2 strains of guinea pigs with genetically determined high and non responsiveness, respectively, to the strong sensitizer 2,4‐dinitrochlorobenzene (DNCB). After skin painting, both strains showed a similar cellular and endocytotic activation of the LCs and a similar intraepidermal localization of DNCB on immunoelectron microscopical visualization. There were however few LC‐lymphoid cell interactions in the non responders, in contrast to numerous such appositions in the other strain. Intravenous tolerization with 2,4‐dinitrobenzene‐l‐sulfonic acid, which is known to block the DNCB receptor of T cells, hampered the lymphoid cell interactions in the DNCB treated high responders, but it did not affect the LC activation. Thesein vivoobservations demonstrate that the hapten‐induced changes of the LC properties is the initial, T‐cell independent event in contac

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1994.tb00288.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractMHC class I and II‐defined, partially inbred miniature swine have recently become available as a large animal model in transplantation immunology. To investigate cutaneous immunocompetence in this model, cutaneous antigen presenting cell (ARC) function was assessed. For morphologic analysis, punch biopsies were examined by electron microscopy. By this technique, epidermal Langerhans cells bearing typical Birbeck granules could be detected. For functional studies, epidermal cell (EC) suspensions were prepared from split thickness skin specimens. Using FACS analysis, freshly prepared epidermal cell suspensions contained 1.8‐4.7% MHC class II‐positive cells. These EC potently stimulated allogeneic nylon wool‐enriched peripheral blood T cells in the primary mixed EC‐lymphocyte reaction. For in vivo assessment of cutaneous APC function. EC suspensions enriched for or depleted of class II‐positive EC were generated by panning of class II‐positive EC using mouse anti‐MHC class II antibodies and anti‐mouse IgG‐coatcd petri dishes. EC were then coupled to the hapten trinitrophenol (TNP) and injected s.c. into autologous or MHC‐mismatched pigs twice at a one week interval. One week later, pigs were challenged by s.c.‐injection of 0.5‐1 × 107TNP‐coupled or uncoupled EC. Autologous unseparated EC as well as EC enriched for MHC class II‐positive cells were able to sensitize naive animals against TNP, whereas neither TNP‐coupled EC depleted of class II‐positive APC, MHC‐mismatched EC coupled to TNP, nor uncoupled EC induced immunity to TNP. Our data indicate that inbred miniature swine possess competent cutaneous APC which are able to induce cutaneous immunity in a manner similar to Lang

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1994.tb00289.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractA variety of tumors are potentially immunogenic but do not stimulate an effective antitumor immune response in vivo. Tumors may be capable of delivering antigen‐specific signals to T cells, but may not deliver the costimulatory signals necessary for full activation of T cells. In this regard, we recently reported that a human melanoma cell line (sMC) expressing MHC class II, was able to induce clonal anergy in a specific, MHC‐restricted CD‐4+ T cell clone (sTC3). We used this system to investigate the influence of interleukin (IL)‐12 on induction of this T cell unresponsiveness. The presence of 10 to 100 U IL‐12 during the induction phase of anergy leads to a primary proliferative response of sTC3, which was significantly higher than that induced by IL‐12 alone; however, in the absence of IL‐12 no proliferation was seen during the induction of anergy. Subsequent optimal stimulation of IL‐12 treated cells, but not of those cultured without IL‐12, led to substantial IL‐2 production and cell proliferation. This indicates that induction of the unresponsive state could be inhibited by IL‐12. In addition, we have recently demonstrated that anergic T cell clones can produce high amounts of 1L‐10 and that this event was correlated with their impaired ability to produce IL‐2. This marked induction of IL‐10 can be suppressed if IL‐12 is present during initiation of unresponsiveness. However, IL‐12 was not able to prime the T cell clone, sTC3, to become resistant against the anergizing stimulus, as this cytokine was only effective when present at the time of anergy induction. These findings indicate that IL‐12 is very effective in preventing anergy when present at the same time as the anergizing stimulus, but is unable to prime T cells to resis

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1994.tb00290.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractIn order to gain insights into the dynamics of mast cell subpopulations in normal and diseased skin, a novel enzyme‐histochemical double and triple staining method was employed that allowed the detection of metachromasia (toluidine blue) and the mast cell proteases tryp‐tase and chymase within the same cell. Cryostat sections were used of skin biopsies from the following specimens: normal skin (N=4), psoriasis (N=13), atopic eczema (N=7), lichen planus (N=6), interferon α2a injection sites (N=l) of a leukemic infiltrate and corresponding normal skin of the same patient before and after treatment. (i) Equal numbers of tryptase‐and chymase‐positive mast cells (MCTC) were obtained in all normal and diseased specimens in papillary and reticular dermis, with threefold increases around appendages, (ii) Tryptase‐positive mast cells (MCT) were absent in normal skin, but were markedly increased in a disease‐specific pattern within the papillary dermis, the inflammatory infiltrate and around appendages, (iii) Marked increases of MCT were also noted at interferon injection sites within the leukemic infiltrate, but not in the normal skin of the same patient. These data suggest that disease‐dependent mast cell dynamics involve only MCT in cutaneous inflammation and that MCT numbers are controlled by distinct, disease‐specific loca

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1994.tb00291.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractTo investigate the interleukin‐8 production of keratinocytes after stimulationin vitrowe have used various agents: (i) contact sensi‐tizer (2,4‐dinitrofiuorobenzene, 3‐n‐penladecylcatechol); (ii) tolerogen (5‐methyl‐3‐n‐pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin‐8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin‐8. Intcrleukin‐8 gene expression was markedly increased upon in vitro stimulation after 1‐6 h with contact sensitizers, tolerogen and the irritant. In contrast, in‐terlcukin‐8 production was not detectable in unstimulatcd normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin‐8 is a response to nonspecific stimuli and may play a critical role in the early response to immuno‐gen

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1994.tb00292.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractIn atopic individuals, allergen‐specific CD4+ T lymphocytes often belong to the T‐helper 2 (Th2) subset as they secrete the marker cylokincs interleukin‐4 (IL‐4) and IL‐5 but not intcrfcron‐y (INF‐y). IL‐10 is a cytokine the production of which, in the mouse system has been described to be restricted to the Th2 subset, but in the human was found to be produced by both ThI and Th2 T cell clones (TCC). We have recently shown that house dust mite antigen (Dermatophagoides pteron‐yssinus)‐specific TCC isolated from skin of patients with atopic dermatitis have a more polarized Th2 cytokine production profile than TCC obtained from the peripheral blood of these patients. In this study, we report that skin‐derived TCC secrete more IL‐10, IL‐4 and IL‐5, than TCC isolated from the blood of the same individual (p<0.05). The difference was more significant with specific TCC than with non‐specific TCC. Furthermore, there was a positive correlation between the production of IL‐10 and that of IL‐4 and IL‐5, respectively. In addition, the amount of IL‐4 and IL‐5 secreted by specific TCC from the skin correlated positively. These results were confirmed by the detection of mRNA by PCR. Finally, our data confirm that in human blood‐derived TCC IL‐10 secretion is not related to a particular cytokine production profile. We suggest that the skin of AD provides an unique environment for the development of aTh2‐likc secretion pattern not only with resp

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1994.tb00293.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThere is strong evidence for a complex network‐like interaction between cytokines, growth factors and other mediators being responsible for cell growth and differentiation as well as for the outcome of an inflammatory reaction. Therefore, the regulation of the production of the ubiquitous proinflammatory cytokine interleukin 6 (IL‐6) by transforming growth factor β (TGFP) was investigated. Human peripheral blood mononuclear cells (PBMC), human normal keralinocytes (HNK), and an epidermoid carcinoma cell line (KB) were treated with TGFβ or TGFβ2 and subsequently IL‐6 secretion was evaluated. Addition of TGFβ1 as well as TGFβ2 to PBMC, HNK and KB cells resulted in a significantly increased release of IL‐6 activity. The inducing effect of TGFβ was dose dependent and maximal when supernatants were harvested 48 h after stimulation. In addition, upon Western blot analysis using a monoclonal IL‐6 antibody significantly increased amounts of IL‐6 protein were detected in KB cell supernatants following stimulation with TGFβ 1. These results were further confirmed at the transcriptional level using a cDNA probe specific for IL‐6 and Northern blot analysis. Accordingly, an increased IL‐6 inRNA expression in PBMC or KB cells was detected following TGFβl treatment. These findings indicate that TGFβ in contrast to its antiinflammatory capacities also may stimulate IL‐6 production in PBMC and keratinocytes. This further supports the possibly important immunoregulatory role of g

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1994.tb00294.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY