Biomedical subjects

M Goebeler

Publications and source records attributed to M Goebeler.

76 records · Page 5Linked to original sources

PubMed1991

Macrophage-derived angiogenesis factors.

A majority of angiogenic factors has been shown to be produced by macrophages. This review will give a concise description of their biochemical nature, their isolation from macrophages and their angiogenic activity. Among the factors with mitogenic effects on endothelial cells are basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF-alpha) and very probably insulin-like growth factor-1 (IGF-1). Other secretory products such as angiotropin and human angiogenic factor (HAF) are nonmitogenic but promote angiogenesis by inducing migration of endothelial cells. Prostaglandins, platelet-derived growth factor (PDGF), granulocyte-macrophage- and granulocyte-colony stimulating factor (GM-CSF, G-CSF), interleukin 6 (IL-6) and angiotensin converting enzyme (ACE) have also been shown to be angiogenic, but their mode of action is still to be clearly defined. As the extracellular matrix appears to be involved in the control of angiogenesis, macrophage-derived factors that can alter this structure via degradation or via the clotting system will also be discussed. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1) and transforming growth factor-beta (TGF-beta) have complex actions on endothelial cells, and can partially inhibit angiogenesis. Among the factors which solely inhibit neovascularization are the interferons. As it is not known whether all of these factors play a role in angiogenesis in vivo attempts to detect them in situ during the course of neovascularization will be described. Finally macrophages will be discussed as cells that may not be mandatory for each phase of the angiogenic process but whose angiogenic capabilities are comprehensive and unsurpassed by any other cell.

Angiogenesis Inducing Agents↗

PubMed1991

Neuropeptides enhance irritant and allergic contact dermatitis.

It is supposed that neuropeptides participate in the regulation of delayed-type hypersensitivity (DTH) reactions. However, their function in this kind of immune response is not known presently. Therefore, in vivo studies were initiated to test the effect on allergic (ACD) and irritant contact dermatitis (ICD) of the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), and somatostatin (SOM), which are released from afferent neurons in the skin. Each neuropeptide was applied topically at the site of contact with the allergen (oxazolone) or irritant (croton oil) during the challenge and sensitization phase of contact dermatitis. The intensity of the inflammation was measured as an increase of ear-swelling response, which represents the degree of plasma extravasation in the early phase of inflammation. Neuropeptides alone led only to a distinct vasodilation. All three neuropeptides were equally able to increase allergic and irritant inflammation. Even minor irritant stimuli were enhanced. Beyond that, CGRP was able to boost sensitization, whereas SOM and SP did not show any effects on the sensitization process. The results presented demonstrate that neuropeptides increase plasma extravasation independent of the pathogenesis of inflammation and may act as priming substances for other mediators of increased vascular permeability. In addition, CGRP enhances the sensitization process.

Animals↗

PubMed1990

Differences in migration inhibitory factor production by C57Bl/6 and BALB/c mice in allergic and irritant contact dermatitis.

Two strains of mice, BALB/c and C57Bl/6, which are known to differ in their inflammatory responsiveness to allergens, were analyzed regarding their expression of macrophage migration inhibitory factor (MIF). Allergic contact dermatitis to 2,4-dinitro-1-fluorobenzene and irritant contact dermatitis to croton oil were studied immunohistologically at designated time intervals after elicitation. BALB/c mice presented a significantly more intense ear swelling response than C57Bl/6 mice and showed a strong endothelial MIF expression in the early phase of inflammation in both allergic and irritant contact dermatitis. Endothelial MIF expression was much weaker in C57Bl/6 mice. Furthermore, the infiltration rate of inflammatory cells (MIF+ and BM8+ macrophages, Lyt2+ and L3T4+ T cells) was significantly higher in BALB/c than in C57Bl/6 mice. We conclude that genetically determined differences of susceptibility to allergens and irritants in BALB/c and C57Bl/6 mice are reflected by the intensity of MIF expression in the microvascular endothelium and immigrating inflammatory cells. MIF seems to appear as first molecular equivalent of developing inflammation and probably determines the degree of cellular infiltration.

Animals↗

PubMed1990

Expression of intercellular adhesion molecule-1 in murine allergic contact dermatitis.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the interaction of immunocompetent cells in inflammation. It contributes to lymphocyte recruitment, antigen presentation and T-cell activation. Recently, the murine homologue of ICAM-1, originally designated as MALA-2, has been identified. The monoclonal antibody YN1/1.7 for murine ICAM-1 enables the analysis of ICAM-1 expression in murine allergic contact dermatitis, a prototype of cutaneous T-cell-mediated inflammatory response. At 0, 1, 8, 24, 48, 72 h, and 7 and 14 days after challenge with 2,4-dinitrofluoro-1-benzene (DNFB) cryostat sections of ear skin were immunostained for ICAM-1, I-A and mononuclear cells (L3T4, Lyt-2, BM8). In normal skin ICAM-1 labeling was restricted to endothelial cells and dermal dendritic cells/macrophages; keratinocytes (KCs) did not express ICAM-1. The dermal cellular infiltrate increased progressively from 8 to 72 h after DNFB challenge. The majority of infiltrating cells were BM8+ macrophages (75%) and L3T4+ (10%) or Lyt-2+ T cells (10%); maximally 30% of those stained positive for ICAM-1. At 24 h, focal ICAM-1 expression on KCs developed, reached a maximum at 72 h and faded thereafter. Migration of T cells into the epidermal layer started at 48 h at sites which had already expressed ICAM-1. Our data provide evidence that expression of ICAM-1 by epidermal cells precedes infiltration of the epidermis by T lymphocytes as shown before in human cutaneous disorders. Thus, a mouse model may be useful to investigate the role of ICAM-1 in inflammation further.

Animals↗