Ultrastructural localization of factor XIIIa

Thin sections of dermatofibromas, of a basal cell epithelioma, a patch stage lesion of Kaposi's sarcoma, a case of angiolymphoid hyperplasia with eosinophilia, and one case of malignant mastocytosis were incubated with antibody to factor XIIIa (FXIIIa). Regardless whether the tissue had been embedded in Lowicryl K4M, Epon, or Araldite, labeling was found in dermal dendrocytes, mast cells, and endothelial cells. In dermal dendrocytes, the reaction product was seen in dilated cisternae of the rough endoplasmic reticulum as well as free within the cytoplasm. In endothelial cells, FXIIIa was localized within Weibel Palade bodies, free within the cytoplasm, and in villous projections into the vasucular lumen. In mast cells, the reaction was found in mast cell granules exclusively. Mast cells, dermal dendrocytes, and endothelial cells have in common that all three express FXIIIa, belong to the microvascular unit, and are increased in number during angiogenesis and in fibrovascular processes. It thus seems that these cells are functionally related.     

Epithelioid cell histiocytoma--histogenetic and kinetics analysis of dermal microvascular unit dendritic cell subpopulations

BACKGROUND: Epithelioid cell histiocytoma (ECH), also known as epithelioid fibrous histiocytoma, is a peculiar dermal tumor, which can mimic melanocytic, vascular, epithelial, or other histiocytic lesions. Thought to arise from dermal dendrocytes, most ECH contain approximately 50% FXIIIa+ histiocytic dendrocytes, but not all lesional cells express FXIIIa. A putative fibroblastic component has not been characterized. METHODS: We analyzed the differentiation and cell kinetics of dermal microvascular unit cells in 12 previously reported ECH using antibodies to FXIIIa, CD68 (KP1), CD34, CD117, CD31, smooth muscle actin, collagen type 1 aminopropeptide, and MIB-1, using single and double immunostains. RESULTS: In ECH, many variably sized CD34/CD31+ tumor vessels with actin+ myopericytes were surrounded by epithelioid-to-dendritic cells of three types. About 5-80% were dendritic histiocytes that expressed FXIIIa but not CD31 or KP1. Fibroblasts, in some cases showing mild nuclear pleomorphism, were usually collagen type 1+, but CD34 and actin- in 11/12 cases. One 'early' ECH had 40% CD34+ epithelioid cells, admixed with 50% FXIIIa+ histiocytes. Most ECH had about 2-20% KP1+, CD117+ mast cells. Mast cell numbers increased with FXIIIa+ histiocyte numbers and the intensity of FXIIIa expression. MIB-1/FXIIIa double-labeling showed only rare cycling histiocytes, with numerous cycling fibroblasts and endothelial cells. CONCLUSIONS: Our findings support the impression that ECH is a vascular fibrous histiocytoma. The constituent cells appear to arise from the activation of resident microvascular CD34+ dermal fibroblasts and the accumulation of FXIIIa+ dendritic stromal assembly histiocytes. The CD34+ cells appear to differentiate toward collagenous fibrocytes in association with histiocytes and mast cells in forming collagenous stroma and vessels. ECH is a tumor composed of all requisite cell types consistent with the origin from the dermal microvascular unit.     

Dermal mast cell granules bind interstitial procollagenase and collagenase.

In order to identify structures in human skin that bind collagenase, sections from frozen or paraffin-embedded skin were incubated with either procollagenase or activated collagenase. After washing, bound procollagenase or collagenase was detected by immunofluorescence microscopy. In normal skin, procollagenase bound only to isolated granular dermal cells that were identified as mast cells on the basis of staining with fluoresceinated avidin and pinacyanol erythrosinate. When mast cells were degranulated by exposure to the ionophore A23187, extracellular granules bound procollagenase. Of various pathologic conditions examined, the highest binding of procollagenase occurred in specimens of urticaria pigmentosa. Procollagenase bound to granular cells and to abundant granules scattered throughout the dermis. Binding could be abolished by pre-treatment of tissue sections with heparinase or by pre-incubation of procollagenase with soluble heparin, suggesting that heparin is the binding agent in the granules. Activated collagenase also bound to dermal mast cells but in addition bound strongly to the dermal collagen. Enzymatic activity of activated collagenase was not inhibited by heparin in concentrations up to 10 mg/ml. There is evidence that mast cell tryptase can contribute to procollagenase activation. This study further supports a role for mast cells in collagenolysis by demonstrating that heparin from mast cells binds procollagenase and possibly serves as a reservoir for procollagenase, which may then subsequently be activated.     

Von Willebrand factor receptor GPIb alpha is expressed by human factor XIIIa-positive dermal dendrocytes and is upregulated by mast cell degranulation.

GPIb alpha, a glycoprotein component of the GPIb-IX-V complex, serves as a platelet membrane receptor that mediates adhesion to von Willebrand factor normally present in the vascular subendothelium. Recent data have demonstrated that GPIb alpha is not restricted to platelets, but is also expressed by endothelium in vitro. In this study, we describe the expression and distribution of GPIb alpha in normal adult and neonatal human skin. GPIb alpha is present, as detected by immunohistochemistry, on endothelial cells and on highly dendritic cells localized within the perivascular space, dermal-epidermal junction, and reticular dermis. By dual-labeling immunofluorescence and confocal microscopy, GPIb alpha-positive cells within the dermal interstitium are demonstrated to represent factor XIIIa-positive dermal dendrocytes. In organ cultures of neonatal human foreskin, mast cell degranulation induced by either substance P or compound 48/80 resulted in transiently increased GPIb alpha expression by dermal dendrocytes. Because the GPIb-IX-V complex plays a part in regulating hemostasis and may be important for cellular interactions with extracellular matrix molecules, these data provide additional insight into the potential function of FXIIIa-positive dermal dendrocytes in skin remodeling and repair.     

Characterization of factor XIIIa positive dermal dendritic cells in normal and inflamed skin

The immunocytochemical identification and characterization of indigenous dermal dendritic cells (dermal dendrocytes) using a rabbit polyclonal antibody to clotting enzyme factor XIII subunit A (FXIIIa) was carried out on normal and inflamed human cutaneous tissue. The immunophenotype of FXIIIa positive dendritic cells was analysed with a panel of 18 monoclonal antibodies using immunoperoxidase and double immunofluorescence staining techniques. The antibody against FXIIIa detected highly dendritic dermal cells located particularly in the upper reticular and papillary dermis. Double fluorescence microscopy showed that FXIIIa positive cells were bone marrow derived (HLe-I+) and co-expressed monocyte, macrophage or antigen presenting cell markers (HLA-DR+, LFA-I+, HLA-DQ+, OKM5+, Mo I+, Mono-I+, Leu M3+). No labelling was obtained with cell markers for Langerhans cells (CDI), T lymphocytes (CD2), granulocytes (LeuMI) fibroblasts (Te7), intercellular adhesion molecule-I (ICAM-I) or endothelial cells (Factor VIII related antigen). Gamma interferon induced increased expression of HLA-DR and co-expression of ICAM-I on FXIIIa+ dermal dendritic cells in normal skin in organ culture. Moreover, in benign inflammatory dermatoses such as atopic eczema and psoriasis there was an increased number of FXIIIa+, DR+, ICAM-I+ cells in the upper dermis and foci of FXIIIa+ cells in the epidermis closely associated with lymphocytes. FXIIIa positive cells in human skin represent a specific population of bone-marrow dermal dendritic cells, distinct from Langerhans cells, that share some features common to mononuclear phagocytes (monocyte/macrophages). In addition, the detection of HLA-DQ on 48% of FXIIIa+ cells and the lack of OKMI in combination with high OKM5 expression suggests an antigen-presenting cell phenotype.     

Case of aquagenic urticaria: Case report and the results of histopathological examination

Aquagenic urticaria (AU) is a rare skin condition in which dermal contact with water serves as a trigger of urticaria and pruritus. To make a diagnosis, a water challenge test is useful. We herein report a 16‐year‐old Japanese boy diagnosed with AU by water provocation test. The induced skin lesion histologically showed prominent degranulation of mast cells and lymphocytic infiltration throughout the dermis. This is the second report documenting the histopathological features of AU.     

Histiocytoma cutis: a tumour of dermal dendrocytes (dermal dendrocytoma)

The histogenesis of histiocytoma (dermatofibroma) was investigated using new antibodies that demonstrate factor XIIIa (FXIIIa) positive cells and the monocyte macrophage cell series (MAC 387), in formalin fixed tissue. The distribution of S100 protein, vimentin and Ulex europaeus agglutinin I (UEA-I) were also studied. The antibody against FXIIIa labelled the normal dermal population of fixed connective tissue cells (dermal dendrocytes) emphasizing their dendritic processes; cells that are widely distributed, but are most numerous in the papillary dermis. In contrast, the antibody, MAC 387 against monocyte derived macrophages, did not label this cell population. In 30 histiocytomas, intense labelling for FXIIIa was found peripherally, but labelling was rather weaker in cells situated centrally. Only a few cells labelled for S100 protein and with the monoclonal antibody MAC 387, but vimentin positivity was universal. UEA-I labelled only vessels in histiocytomas. However, FXIIIa labelling was negative in 16 dermatofibrosarcomas, three keloids and several other fibroproliferative lesions. These contrasting results with FXIIIa labelling have practical implications for diagnosis of benign and malignant spindle cell tumours of the skin. We conclude that histiocytomas (dermal dendrocytomas) take their origin from dermal fixed connective tissue cells, (dermal dendrocytes), but other spindle cell tumours may differ in histogenesis.     

The presence of tryptase-positive and bikunin-negative mast cells in psoriatic skin lesions

Human mast cells are well known to produce a serine protease, tryptase, which appears to play a pathogenic role in various skin inflammations. It was previously reported that a rat homologue of bikunin may inhibit tryptase activity. Various type of cells (i.e. keratinocytes) are able to produce this protein inhibitor, it still remains unclear if bikunin is present in dermal inflammatory milieu, in which mast cells, through secretion of tryptase, play an inflammatory role. Therefore, the purpose of the present study was to exploit expression and production of bikunin in dermis and dermal constituents. We first compared the dermal mast cells in psoriatic lesions with those in lesional skin of atopic dermatitis or of chronic eczema by use of immunoelectron microscopy and immunohistochemical analyses using antibodies to bikunin and tryptase. Then, we tested what kinds of cytokines may regulate the de novo synthesis of bikunin. To do so, RNA was extracted from a human mastocytic cell line, HMC-1, reverse-transcribed, and semiquantitative RT-PCR was performed using primers specific for bikunin. With immunoelectron microscopy, bikunin was found to localize on the cell membrane, while tryptase was in the secretary granules of the mast cells. In psoriatic lesions, around 70% of dermal mast cells were positive for both tryptase and bikunin, and the remaining was mostly positive for tryptase, but the expression of bikunin was under the detection limit of the experimental setting. This observation was seen in only psoriatic lesions, even in almost cured lesions, while in atopic dermatitis or chronic eczema only mast cells doubly positive for bikuin and tryptase were seen. In HMC-1, bikunin was constitutively expressed at an mRNA level, which was upregulated by stimulation with interleukine-4, but was suppressed by interferon-γ. Bearing in mind the concept that in psoriasis local cytokine milieu is shifted toward a Th1 pattern (predominant secretion of interferon-γ), tryptase-positive, bikunin-negative mast cells may be induced.     

Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique

Summary The aim of the present study was to test further our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic. For this purpose, contact sites between mast cells and sensory nerves were morphometrically analysed in the basement membrane zone, papillary dermis and three dermal zones of lesional/non-lesional psoriatic and lichen planus skin as well as in healthy control skin. The analyses were made on sections stained with a histochemical double stain developed for this study. With the double stain, active mast cell tryptase was stained blue enzyme histochemically, and the sensory nerves black using specific monoclonal anti-neurofilament antibodies with immunogold. In psoriatic lesions, both mast cells and mast cell — nerve contacts were markedly more frequent in the basement membrane zone and in the papillary dermis when compared with the corresponding areas in the other groups. Mast cell numbers were increased in both lesional and symptom-free skin in lichen planus, but no increase was found in the mast cell — nerve contacts. Increased contacts between mast cells and sensory nerves indicate that the elements exist for neurogenic inflammation in psoriatic lesions. These increased contacts are not due to the extensive inflammatory reaction only, because they were not observed in lichen planus lesions.     

Ultrastructural findings in tissue mast cells in urticaria pigmentosa

In a study on 10 patients suffering from urticaria pigmentosa, biopsies of skin lesions were electron microscopically investigated. In contrast to normal skin, the mast cells showed irregular, partly bilobed nuclei, prominent nucleoli, hypogranulation, and rather small granules; giant granules were rarely observed. In addition, we frequently found degranulation, and the development of microvilli was much more prominent than with normal mast cells. These deviations from normal skin represent at least in part functional alterations. However, some of the findings suggest that urticaria pigmentosa may be considered a neoplastic disease of the tissue mast cells, although clear evidence is still lacking. In any case, our findings show that mast cells in mastocytosis are not identical with those in normal skin.     

Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skin

Background Senile lentigo (SL) is a pigmentation disorder that occurs predominantly on the dorsa of the hands, the forearms and the face; its incidence increases with age. Histological hallmarks of SL lesions are hyperpigmentation of the epidermis and elongation of the epidermal rete ridges. Various factors such as α‐melanocyte‐stimulating hormone, endothelin‐1 or stem cell factor are involved in the onset and maintenance of the increased pigmentation. Alterations of the dermal compartment have not yet been analysed in detail in SL. Objectives To study the occurrence and distribution of melanin in the dermis from SL and aged skin, biopsies from 12 subjects were morphologically analysed by light and electron microscopy in comparison with unaffected skin. Methods Punch biopsies of SL and adjacent skin from 12 male or female volunteers aged 52–81 years were prepared for light and electron microscopy and samples were analysed by morphological, morphometric, histochemical and immunohistochemical methods. Results The epidermis from SL revealed morphological features such as hyperpigmentation of basal keratinocytes and the formation of elongated rete ridges. S100+ melanocytes in the stratum basale were not markedly increased, indicating that the hyperpigmentation is predominantly due to changes in melanin synthesis, distribution or turnover. Quantification of epidermal cells expressing the proliferation marker Ki67 did not show an increase of this parameter in SL, indicating that at least in the established lesion cell proliferation is not enhanced. We further focused on the dermal compartment and observed granulated cells which were more abundant in SL. Electron microscopic and histochemical analysis revealed that the granulation of these cells is based on melanosomes, mostly present in large melanosomal complexes. Immunohistochemistry using antibodies to CD68 and factor XIIIa (FXIIIa) showed these melanophages to be predominantly FXIIIa+ dermal dendrocytes, which were about six times more abundant than CD68+ macrophages. Conclusions In SL an increased number of melanophages was found compared with unaffected skin from the same subject. These melanophages were identified as FXIIIa+ dermal dendrocytes. Possible functional consequences of the massive melanin uptake by dermal dendrocytes are discussed.     

Inhibitory effects of antipsychotic and anxiolytic agents on stress‐induced degranulation of mouse dermal mast cells

Background. Various psychological stresses induce degranulation of mast cells. It has been confirmed by animal experiments that stress induced by restraint promotes mast‐cell degranulation in various organs, and that the degranulation is inhibited by pretreatment with corticotropin‐releasing factor (CRF)‐neutralizing antibodies, CRF receptor antagonists, and neurotensin (NT) antagonists. Previous studies have suggested that anxiety and fear induced in animals by psychological stressors promote the production and release of various neuropeptides and neurotransmitters, and induce degranulation of mast cells in several organs. Aim. To evaluate the effect of prior treatment with antipsychotic and anxiolytic agents to inhibit foot‐shock (FS) stress‐induced degranulation of mouse dermal mast cells. Methods. Using a communication box system, FS was administered to mice and the degranulated dermal mast cells were counted. Chlorpromazine (2 or 4 mg/kg body weight), tandospirone (10 mg/kg body weight) or CRA1000, a selective non‐peptidic CRF receptor type 1 antagonist (10 or 100 mg/kg body weight) was injected intraperitoneally 1 h before exposure to FS. Results. After FS was administered, the number of dermal mast cells did not change. However, FS significantly increased the proportion of degranulated mast cells. Pretreatment of mice with chlorpromazine hydrochloride, an antipsychotic agent (2 or 4 mg/kg), or the anxiolytic agents tandospirone citrate (10 mg/kg) or CRA1000 (10 or 100 mg/kg), significantly inhibited the FS‐induced mast‐cell degranulation (P < 0.05, P < 0.01, P < 0.05, P < 0.05, and P < 0.05, respectively). Conclusions. Antipsychotic and anxiolytic agents may be effective treatments for stress‐aggravated inflammatory skin diseases by inhibition of mast‐cell degranulation.     

Rat skin main neutral protease: immunohistochemical localization.

Specific antiserum against the purified rat skin main neutral protease was used in double layer immunofluorescent method to localize the enzyme in normal rat skin. The specific immunofluorescence was seen in dermal cells that were identified as mast cells on basis of their metachromatic granules. Enzyme histochemical staining with naphthol AS-D chloroacetate localized to the same cells that exhibited specific immunofluorescence. The granules of isolated rat mast cells also gave a specific reaction with the immunohistochemical technique. The results provide further evidence for the suggestion that rat skin main neutral protease is identical with the rat mast cell "chymase."     

Fibrous mastocytoma in a patient with generalized cutaneous mastocytosis

A 57-year-old woman with cutaneous mastocytosis of 23 years duration developed a hyperpigmented abdominal plaque composed of confluent indurated papules that enlarged for a period of 1 year to 12 x 8 cm. Biopsy showed dermal infiltration by closely packed spindle-shaped mast cells, fibroblasts, collagen, and scattered lymphocytes, predominantly T-suppressor cells. Electron microscopy showed close contact between mast cells, fibroblasts, and lymphocytes. Piecemeal mast cell degranulation and extrusion of mast cell granules was seen, with rare mast cell granules in fibroblasts, and collagen fibers in peripheral and perinuclear endoplasmic reticulum of mast cells. the term Fibrous mastocytoma is suggested for this tumor-like dermal fibrosis, possibly induced by lymphokines.     

Cytological alterations in dermal dendrocytes in vitro: evidence for transformation to a non-dendritic phenotype

Dermal dendrocytes (DDs) are bone marrow-derived cells which are abundant in normal human and murine dermis, where they are closely associated with mast cells in the perivascular space. The biological role of DDs remains enigmatic. DDs express coagulation factor XIIIa and the recently described von Willebrand factor receptor, GPIb alpha, potentially indicating a function in tissue repair and haemostasis, although participation in antigen presentation is also speculated. In healing wounds and 'fibrohistiocytic' tumours, such as dermatofibromas, DDs are often associated with non-dendritic histiocytes, some of which also express factor XIIIa (FXIIIa). We have utilized human skin organ culture to examine the effects of various biological mediators on cytological characteristics of DDs. It was found that by 24 h in organ culture, immunoreactive DDs begin to lose their dendritic shape, assuming more rounded contours. This phenomenon was accentuated by mast cell degranulation; was independent of the nature of mast cell secretagogue; and could not be reproduced by recombinant tumour necrosis factor-alpha, a cytokine known to increase FXIIIa expression in DDs. Like their dendritic precursors, non-dendritic cells expressed variable FXIIIa, CD34 and CD68 and did not express CD1a or CD45. By ultrastructure, non-dendritic cells that develop in vitro resembled non-degenerating monocytes containing occasional primary lysosomes and lipid inclusions, and like DDs, expressed fibronexus-like plaques on the cell membrane. Transition of DDs from dendritic to non-dendritic cells as a consequence of specific microenvironmental influences may provide insight into the frequent concurrence of these two cytological types in fibrohistiocytic tissue reactions and neoplasia.     

Release of soluble tryptase but only minor amounts of chymase activity from cutaneous mast cells

Tryptase and chymase are the major serine proteinases of skin mast cells but their biologic significance depends on their activity. In this study, we demonstrate the release of soluble activity of tryptase, but not markedly that of chymase, into skin blister fluids induced by freezing with liquid nitrogen as well as into supernatant during incubation of 8 whole skin specimens with compound 48/80 for up to 2 days followed by sonication. Incubation of 3 other skin specimens in compound 48/80 for up to 2 days revealed that the number of mast cells displaying tryptase activity decreased significantly on day 2, and the number of mast cells showing chymase activity (but not those showing chymase immunoreactivity) decreased significantly on day 1 but not thereafter on day 2. The results of 3 skin organ cultures for up to 14 days showed steady decrease in the number of tryptase-positive cells but persistence of mast cells containing chymase activity. Chymase in solution was sensitively inhibited by 0.01 mg/ml alpha1-antichymotrypsin but higher concentrations (0.3-3.0 mg/ml) were needed for inhibiting chymase on skin sections. In conclusion, after mast cell degranulation tryptase activity is substantially solubilized and it may potentially affect both local and distant skin structures. Instead, chymase is partially inactivated and the remaining chymase activity persists at the site of degranulation having only local effects.     

Mast cell changes in a case of rapidly progressive scleroderma-ultrastructural analysis

A 63-year-old woman had rapidly progressive scleroderma and died 4 months after the clinical appearance of her illness. Extreme itching of the affected skin was prominent. Electron microscopic study of the clinically uninvolved skin showed mainly normal mast cells. Mast cells in clinically involved skin showed a wide morphologic spectrum including evidence of cellular activation. There was an increased amount of cytoplasm occupied by polysomes and mitochondria and less cytoplasm occupied by granules. Most granules were pale and swollen, suggesting active degranulation. In some cases it was difficult to distinguish a hyperactive mast cell with only a few granules remaining from a fibroblast which had acquired granules by transgranulation. This case illustrates the active participation of mast cells in acute scleroderma.     

Formalin sensitivity and differential staining of mast cells in human dermis

The characteristics of the human dermal mast cell population with respect to formalin fixation sensitivity, toluidine blue staining and alcian blue/safranin staining were studied. Thirty-seven specimens of normal human skin were bisected. One half was fixed in 10% neutral buffered formalin and the other in Carnoy's fixative. Sections were cut and stained with either toluidine blue or alcian blue/safranin. Significantly more mast cells were visualized with alcian blue/safranin than with toluidine blue. With both stains, only approximately 50% of the mast cells observed in the Carnoy's fixed tissue could be visualized in the formalin-fixed tissue. Alcian blue/safranin staining revealed three patterns of mast cell granule staining: mast cells containing only alcian blue-positive granules, mast cells containing only safranin-positive granules, and mast cells containing a mixture of alcian blue-positive granules and safranin-positive granules. Mast cells containing only alcian blue-positive granules constituted the majority of the dermal mast cell population and 73% of these mast cells were formalin-sensitive. Mast cells containing only safranin-positive granules and those containing a mixture of alcian blue-positive granules and safranin-positive granules showed no evidence of formalin sensitivity. The human dermal mast cell population, therefore, displays heterogeneity with respect to formalin fixation sensitivity and alcian blue/safranin staining. Dermal mast cells were visualized in significantly greater numbers in skin from the head compared with that from the body or limbs.     

Extracellular localization of human connective tissue mast cell granule contents.

In early phases of cutaneous inflammation, connective tissue mast cell degranulation is associated with apparent secretion and externalization of immunoreactive chymotryptic serine proteinase. To determine whether this event is associated with structural evidence of granule externalization, we studied the sequential evolution of IgE-mediated hypersensitivity in vivo, as well as mast cell degranulation provoked by a variety of stimuli in cultured explants of human skin. By 1 min after intradermal antigen challenge with ragweed extract, mast cell degranulation was associated with apparent extrusion of intragranule constituents into the pericellular connective tissue. Similar features typified cultured skin explants exposed for 45 min to anti-IgE and other mast cell secretagogues (morphine sulfate, calcium ionophore A23187, compound 48/80, and substance P). Once externalized, granule constituents could be identified within the dermal matrix by their rounded contour and structural similarity to solubilized granule matrices remaining within actively secreting cells. These data indicate that externalization of connective tissue mast cell granule contents occurs early after secretagogue exposure, potentially accounting for infrequent documentation of this event in naturally occurring dermatoses. The ability to recognize externalized granule products at a morphologic level should facilitate the understanding of interactions between mast cell-derived mediators and target structures of the dermal microvasculature.     

The inflammatory response in drug-induced acute urticaria: ultrastructural study of the dermal microvascular unit

BACKGROUND: Drug exposure is one of the main aetiologies of urticaria and represents the second most common cause in acute urticarias. Studies involving the ultrastructural aspects of urticaria are relatively rare in the literature. Most of the articles published report on skin biopsies of experimentally induced urticaria, and acute urticaria has been studied even less from a morphological point of view. OBJECTIVES: The aims of this study were to observe ultrastructural cell characteristics in five patients with drug-induced acute urticaria and possible aspects of the inflammatory skin response. METHODS: Clinical manifestations, light microscopy and transmission electron microscopy were evaluated. RESULTS: With light microscopy, a mild perivascular lymphocyte-monocyte infiltrate was observed with few neutrophils and dermal oedema in skin biopsies of five patients. With electron microscopy, a mild vascular dilatation was observed, with platelets in the lumen and several lymphocytes and dendritic cells close to the superficial dermal vessels. Some mast cells appeared normal, whereas others were granule-depleted. In some areas, mast cells, lymphocytes and satellite dendritic cells were closely associated, as well as some macrophages. A significant number of plasma cells, eosinophils and polymorphonuclear neutrophils were not observed; however, the presence of lymphocytes and macrophages was significant. The epidermis and the dermal-epidermal junction were preserved, except for a discrete oedema in keratinocytes. CONCLUSIONS: The ultrastructural aspect of drug-induced acute urticaria is similar to that observed in urticaria caused by Urtica dioica, intradermal histamine and cold urticaria. The presence of the cellular triad with mast cells, dendritic (or satellite) cells and lymphocytes suggests a functional interaction of these cells. These findings support the possible existence of mechanisms in the dermis that may participate in protective and/or injurious vasocentric immune reactions.