ABSTRACT
We have previously found that ability of mouse macrophages to bind and take up oxidized low-density lipoprotein (oxLDL) through scavenger receptors is significantly enhanced when the cells are plated on fibronectin (FN)-coated culture substrates. Here, the mechanisms of the enhancement of the scavenger receptor activity by the substrate-bound FN was investigated using thioglycollate-induced mouse peritoneal macrophages. A Ca(2+) channel blocker diltiazem and a calmodulin inhibitor W-7 reduced the scavenger receptor activity of the macrophages plated on FN-coated substrate to the level of the cells plated on uncoated substrate, as assessed by oxLDL binding, while the scavenger receptor activity of the macrophages on uncoated substrate was little affected. Similarly, FN-induced enhancement of the scavenger receptor activity assessed by oxLDL uptake was selectively inhibited by Ca(2+) channel blockers (diltiazem, nifedipine, verapamil) and calmodulin inhibitors (W-7, trifluoperazine). Intracellular free Ca(2+) level of the macrophages was increased, depending on extracellular Ca(2+), when plated on FN-coated substrate. This increase in the Ca(2+) level was inhibited by diltiazem and RGD-containing peptides present in cell adhesive region of FN. Like the substrate-bound FN, Ca(2+) ionophore A23187 enhanced the scavenger receptor activity of binding and taking up of oxLDL. These results indicate that substrate-bound FN enhances scavenger receptor activity of macrophages by increasing channel-dependent Ca(2+) influx. A microtubule disruptor, colchicine, and an actin filament disruptor, cytochalasin B, inhibited the FN-induced enhancement of the scavenger receptor activity, suggesting that these cytoskeletal structures are required for transmission of the adhesion signal of FN. The number of the scavenger receptors was found to increase by 1.4-fold upon adhesion signal of FN. We suggest that substrate-bound FN increases the number of the macrophage scavenger receptors as a result of induction of Ca(2+) influx and causes increased accumulation of oxLDL within the cells, rendering the cells more susceptible to conversion into foam cells.
Subject(s)
Calcium Signaling/physiology , Calcium/metabolism , Fibronectins/metabolism , Macrophages/metabolism , Membrane Proteins , Receptors, Immunologic/metabolism , Receptors, Lipoprotein , Animals , Biological Transport , Calcimycin/pharmacology , Calcium Signaling/drug effects , Cattle , Cytoskeleton/drug effects , Humans , In Vitro Techniques , Ionophores/pharmacology , Macrophages/drug effects , Male , Mice , Receptors, Immunologic/drug effects , Receptors, Scavenger , Scavenger Receptors, Class BABSTRACT
Clobetasol-17-propionate (CP), a synthetic glucocorticoid (GC), reduced skin thickness in rats. Both the subcutaneous injection and topical applications of RU 486 counteracted CP-induced reduction in skin thickness. Topical application of the CP cream completely inhibited the ear edema produced by croton oil. A less potent GC, hydrocortisone-17-butyrate, also inhibited ear edema. This antiinflammatory effect was not abolished by the subcutaneous injection or topical application of RU 486. These observations suggest that GC-induced skin atrophy is mediated by glucocorticoid receptors (GRs), while the inhibition of croton oil-induced inflammation by GC is primarily related to the direct effects of GC, which are not mediated by GRs. Our findings suggest that RU 486 inhibits the atrophogenic effect of GCs without interfering with their antiinflammatory effect. Dissociation of antiinflammatory and atrophogenic activity of GC seems favorable in treating inflammatory skin diseases lacking epidermal proliferation.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Glucocorticoids/antagonists & inhibitors , Glucocorticoids/pharmacology , Mifepristone/pharmacology , Skin/drug effects , Skin/pathology , Animals , Atrophy , Clobetasol/analogs & derivatives , Clobetasol/pharmacology , Croton Oil , Dexamethasone/metabolism , Ear Diseases/chemically induced , Ear Diseases/drug therapy , Edema/chemically induced , Edema/drug therapy , Ligands , Male , Rats , Rats, Wistar , Receptors, Glucocorticoid/metabolism , Skin/metabolismABSTRACT
An 85-year-old Japanese man with Bowen's disease on the left inguinal area is reported. Most of the inflammatory cells adjacent to the tumor were eosinophils. Tissue eosinophilia spontaneously improved after biopsy.
Subject(s)
Bowen's Disease/pathology , Eosinophils/pathology , Skin Neoplasms/pathology , Aged , Aged, 80 and over , Humans , Male , Skin/pathologyABSTRACT
We report a 62-year-old woman with acquired tufted angioma. Several scattered reddish nodules were present on the neck and upper chest. During a follow-up period of 6 months, some of the lesions showed transient spontaneous regression and one disappeared completely. Electron microscopy revealed that a few tumour cells contained Weibel-Palade bodies in their cytoplasm.
Subject(s)
Hemangioma/pathology , Plant Lectins , Skin Neoplasms/pathology , Female , Hemangioma/ultrastructure , Humans , Immunohistochemistry , Lectins/analysis , Middle Aged , Remission, Spontaneous , Skin Neoplasms/ultrastructure , von Willebrand Factor/analysisABSTRACT
We report a case of angiosarcoma with some peculiar clinical features developing on the left thigh of a 63-year-old man. The early primary lesion was erythematous with necrotic areas. The initial biopsy specimen of the lesion indicated a benign angioproliferative process. However, the necrotic area enlarged rapidly, ulcerated with severe pain, and thus was widely excised. The excised specimen had a malignant histologic appearance, particularly in the fascia, and was diagnosed as angiosarcoma. Following local recurrence, the lesion was complicated by thrombosis of the femoral artery at the affected site. A similar cutaneous lesion subsequently arose on the right lower leg, and thrombosis developed in the right femoral artery. Both legs had to be amputated. There were no distant metastases.
