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Biomedical subjects

C Pincelli

Publications and source records attributed to C Pincelli.

At least 19 recordsLinked to original sources
PubMed1995

Nerve growth factor receptor and neurochemical markers in human oral mucosa: an immunohistochemical study.

BACKGROUND: The innervation of the oral mucosa has so far been studied mainly by histochemical and ultrastructural techniques. Only few studies have investigated the presence of neural proteins and neurotransmitters in human gingival mucosa. OBJECTIVE: The purpose of the present study was to evaluate the presence and distribution of neural structural and transmitter proteins in different areas of normal human oral mucosa. METHOD: Indirect immunofluorescence was employed on specimens taken from different mucosal regions (gingiva, lips, gums, palate). Both structural (low-affinity nerve growth factor receptor, NGFr; protein gene product 9.5, PGP 9.5) and neuropeptide markers (substance P; calcitonin gene-related peptide; vasoactive intestinal peptide, neuropeptide Y) were used. RESULTS: NGFr and PGP 9.5 intensely labelled both nerve fibres and selected epithelial cells, while neuropeptide immunoreactivity was scarcely expressed and exclusively localized in nerve fibres. CONCLUSIONS: Similarly in the distribution pattern and neurochemistry between oral and cutaneous innervation is apparent. Expression of NGFr could be relevant to the trophism of both the oral innervation and epithelium.

Adolescent↗
PubMed1994

Expression and function of nerve growth factor and nerve growth factor receptor on cultured keratinocytes.

Keratinocytes, a key cellular component both for homeostasis and pathophysiologic processes of the skin, secrete a number of cytokines and are stimulated by several growth factors. Nerve growth factor (NGF) is synthesized in the skin and basal keratinocytes express the low-affinity nerve growth factor receptor (NGF-R). We present evidence that normal human keratinocytes in culture express the low- and the high-affinity NGF-R both at the mRNA level, as determined by reverse-transcription polymerase chain reaction and at the protein level, as shown by cytofluorimetric analysis. NGF significantly stimulates the proliferation of normal human keratinocytes in culture in a dose-dependent manner. This effect can be prevented by the addition of both an anti-NGF neutralizing antibody and a high-affinity NGF-R (trk) specific inhibitor, the natural alkaloid K252a. By contrast, keratinocyte proliferation is not inhibited by an anti-low-affinity NGF-R monoclonal antibody, thus suggesting that NGF effect on human keratinocytes is mediated by the high-affinity NGF-R. Moreover, NGF mRNA is expressed in normal human keratinocytes and NGF is secreted by keratinocytes in increasing amounts during growth, as detected by enzyme-linked immunosorbent assay. These results suggest that NGF could act as a cytokine in human skin and take part in disorders of keratinocyte proliferation.

Antibodies, Monoclonal↗
PubMed1994

Psoriasis and the nervous system.

Both clinical and experimental evidence is accumulating on the role of the nervous system in the pathogenesis of psoriasis. Sporadic reports as well as extensive studies indicate that emotional stress can act as an exacerbating event in psoriasis. Moreover, that neurogenic mechanisms are operating in psoriasis is suggested by clinical, pharmacologic and experimental data. We have focused our investigations on the role of vasoactive intestinal peptide (VIP) and substance P (SP) in psoriatic lesions using a variety of experimental approaches: 1) receptor autoradiography; 2) immunohistochemistry; 3) radio-immunoassay; 4) human keratinocytes cultures. Our results indicate that an imbalance of VIP and SP exists in psoriatic lesions, and that these neuropeptides exert different and specific effects on human keratinocytes. At present, however, the finding of psoriasis being exacerbated by psychological factors cannot be satisfactorily explained merely by alterations of neuropeptides in the skin.

Humans↗
PubMed1993

Autoradiographic detection of substance P receptors in normal and psoriatic skin.

Substance P has been detected in human skin and has been implicated in the pathogenesis of certain inflammatory cutaneous disorders. However, little is known about the number and distribution of substance P binding sites in the skin. Receptor autoradiography was employed to detect and quantitate substance P receptors in normal as well as psoriatic skin. Substance P binding sites were distributed in the epidermis and dermis both in normal and psoriatic skin. In the dermis, the highest densities of SP binding sites were found in the areas corresponding to the dermal papillae and the adnexal structures. Quantitative analysis revealed that saturable binding was obtained both in the epidermis and in the labeled dermal areas. Rosenthal plot values were consistent with a single population of binding sites. No difference in the binding measurements was observed between normal and psoriatic skin. The presence of substance P receptors in the epidermis and in the dermal papillae raises interesting issues on the possible targets of this peptide in human skin both under physiologic and pathologic conditions.

Autoradiography↗
PubMed1993

Neuropeptides and skin inflammation.

Neuropeptides (NP) are protein compounds contained both in the central and peripheral nervous system. They can be antidromically released from sensory nerves and are implicated in the so-called neurogenic inflammation. They also exert a number of functions within the immune system and are thought to act as trophic as well as mitogenic substances. Several NP have been detected in human skin by immunohistochemical and radioimmunological techniques, and recent reports have demonstrated that NP could be involved in the mechanisms of certain dermatoses. The involvement of NP in either physiological or pathophysiological skin conditions is discussed. Moreover, a few questions, which still need to be addressed, are raised, and future directions this field of research should take are outlined.

Calcitonin Gene-Related Peptide↗
PubMed1992

Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured human keratinocytes.

An involvement of neurogenic components in the pathogenesis of psoriatic lesions has been suggested and neuropeptides are thought to play a modulatory role in cutaneous inflammation. In this study, we evaluated the immunoreactivity of the neuropeptides vasoactive intestinal polypeptide (VIP) and substance P (SP) in the skin of patients with chronic plaque psoriasis, by immunohistochemistry and radioimmunoassay. No differences were observed, by immunohistochemistry, in the expression and localization of VIP and SP between psoriatic and normal skin. Using the radioimmunologic technique on whole skin homogenates, VIP levels were significantly increased in psoriatic lesions as compared to normal skin. By contrast, SP levels were significantly lower in lesional and non-lesional psoriatic skin than in normal skin. In addition, we examined the effect of VIP and SP on the proliferation of cultured normal human keratinocytes. VIP (1-28) (1 nM-1 microM) as well as VIP fragments (10-28) (1 nM-1 microM) and (22-28) (1 nM-1 microM) stimulated the proliferation of keratinocytes in a dose-dependent manner, whereas the VIP fragment (1-12) (1 nM-1 microM) was ineffective. The VIP antagonist (N-Ac-Tyr1, D-Phe2)-GRF (1-29)-NH2 (0.1 microM) significantly inhibited the VIP effect on keratinocytes. On the other hand, SP (0.1 microM) not only failed to stimulate keratinocyte growth, but also blocked the VIP-induced stimulation of these cells. The imbalance of cutaneous VIP and SP and their disparate effects on the proliferation of normal human keratinocytes in culture would suggest that these peptides are involved in the pathogenesis of psoriasis and may exert different modulatory activities in the mechanisms underlying the psoriatic lesion.

Cell Division↗
PubMed1992

Substance P levels are decreased in lesional skin of atopic dermatitis.

There is increasing evidence that neuropeptides (NP) such as substance P (SP) and vasoactive intestinal polypeptide (VIP) are involved in the pathogenesis of atopic dermatitis (AD). Vasoactive intestinal polypeptide levels were found to be significantly elevated in lesional skin of AD as compared to controls. We evaluated by radioimmunoassay the SP content in whole skin homogenates from chronic lichenified lesions of patients with AD. The levels of SP were significantly decreased in lesional skin from AD patients as compared to control skin (0.25 +/- 0.03 vs. 0.97 +/- 0.24 pmol/g tissue, p < 0.01). The diminished SP levels as opposed to increased VIP concentrations could be consistent with different roles of these NP as modulatory agents in the mechanisms associated with AD.

Adolescent↗
PubMed1992

Vasoactive intestinal polypeptide and substance P in the pathogenesis of atopic dermatitis.

Neurogenic components are probably involved in the pathogenesis of atopic dermatitis (AD) and several neuropeptides have been implicated in the mechanisms underlying this disease. The aim of the present study was to evaluate by radio-immunoassay (RIA), the vasoactive intestinal polypeptide (VIP) and substance P (SP) content in whole-skin homogenates of AD lesions. RIA was performed using an antiserum, AH78, recognizing the carboxy-terminal fragment VIP (22-28) and a polyclonal antiserum directed against SP. VIP levels were markedly increased in lesional AD skin (5.62 +/- 1.25 pmol/g tissue) vis-à-vis controls (0.43 +/- 0.08 pmol/g tissue), whereas SP levels were significantly lower in lesional skin (0.25 +/- 0.03 pmol/g tissue) than in normal skin (0.97 +/- 0.24 pmol/g tissue). The results confirm that VIP and SP are relevant to the pathogenesis of AD and their imbalance might reflect diverse roles of these NP in the modulation of AD lesion.

Adolescent↗
PubMed1992

Cutaneous innervation in chronic renal failure patients. An immunohistochemical study.

Most chronic renal failure patients suffer from generalized pruritus. An involvement of cutaneous nerve terminals in the pathogenesis of uremic pruritus has been suggested. Skin specimens from 24 uremic patients and 10 healthy subjects were processed with an indirect immunofluorescence method to investigate the presence and distribution of a number of neuronal markers and neuropeptides. No difference was found between the two groups in the distribution pattern of the positive nerve fibres. However, a reduction in the total number of skin nerve terminals in the uremic patients was detected. No correlation could be found between the immunohistochemical findings and the clinical features. Our results suggest that the skin innervation is altered in most chronic renal failure patients, possibly as a consequence of neuropathy.

Adult↗
PubMed1991

Skin levels of vasoactive intestinal polypeptide in atopic dermatitis.

Atopic dermatitis (AD) can be exacerbated by various factors, including emotional stress, scratching and sweating. The aim of the present study was to evaluate the hypothesis that the inflammatory reaction in AD is also neurogenic. For this purpose, the levels of vasoactive intestinal polypeptide were measured radioimmunologically in whole-tissue homogenates of lesional skin of 13 patients with atopic dermatitis. Radioimmunoassay was performed using an antiserum, AH78, recognizing the carboxy-terminal fragment vasoactive intestinal polypeptide (22-28). Vasoactive intestinal polypeptide immunoreactivity was detected in relatively low amounts in control skin (0.428 +/- 0.08 pmol/g tissue), whereas a marked increase in the peptide was observed in lesional skin of patients with atopic dermatitis (5.62 +/- 1.25 pmol/g tissue). These results seem to suggest that vasoactive intestinal polypeptide could have a pathogenetic relevance in skin lesions of atopic dermatitis.

Adolescent↗
PubMed1991

Immunohistochemistry of cutaneous graft-versus-host disease after allogeneic bone marrow transplantation.

Graft-versus-host disease (GVHD) is an immunologically mediated disease occurring most frequently after allogeneic bone marrow transplantation. The aim of this study was to evaluate the contribution of immunohistochemistry in the diagnosis of cutaneous GVHD. Patients transplanted for either leukemia or beta-thalassemia were included in the study. Skin lesions of acute and chronic GVHD were examined both by direct immunofluorescence to detect immunoglobulin deposits and by an avidin-biotin-peroxidase complex technique to evaluate the inflammatory cell infiltrate. Epidermal and dermal fluorescent bodies (IgG and IgM) were frequently found in both acute and chronic GVHD. Most of the infiltrating cells were CD3+ T lymphocytes, with CD8+ cells representing the major cell population invading the epidermis both in acute GVHD and in chronic lichenoid GVHD. A small proportion of the dermal cells were CD14+ macrophages; no B cells were detected. HLA-DR, but not HLA-DQ antigens, were variably expressed by keratinocytes in all cases of acute GVHD and in chronic lichenoid GVHD. KL-1, a monoclonal antikeratin antibody specific for the 56.5 KD acidic polypeptide usually present in suprabasal keratinocytes, stained all epidermal layers, including the basal layer. Langerhans cells were dramatically reduced in number in the epidermis of both acute and chronic lichenoid GVHD. It is concluded that immunohistologic analysis may be supportive in the diagnosis of acute and early chronic lichenoid cutaneous GVHD.

Acute Disease↗
PubMed1990

Neuropeptides in skin from patients with atopic dermatitis: an immunohistochemical study.

The distribution and localization of several neuropeptides were investigated in the lichenified lesions of 11 patients with atopic dermatitis using indirect immunofluorescence. Substance P-positive nerve fibres were observed in most of the cases of atopic dermatitis, but not in normal controls. Somatostatin immunoreactive nerves were not found in the skin of atopic dermatitis, whereas a normal pattern of immunoreactivity could be detected in most of the healthy subjects. Neuropeptide Y-positive dendritic epidermal cells were observed in lesional skin from patients with atopic dermatitis, but not in controls. Calcitonin gene-related peptide and vasoactive intestinal polypeptide immunoreactivity in patients with atopic dermatitis did not differ from that in healthy subjects. With galanin antiserum a diffuse intracellular staining was observed in the epidermis of both atopic patients and controls, while no positive staining was found with either neurotensin or neurokinin A antibodies in either group. These findings suggest a possible involvement of some neuropeptides in the pathomechanisms of atopic dermatitis.

Adolescent↗
PubMed1990

Relationship between NK cells and granulomatous inflammation in mice.

The relationship between natural killer (NK) cells and granulomatous inflammation was investigated using two experimental granuloma models in C57BL/6 mice. The hepatic granuloma model was produced by infection with Schistosoma mansoni (S. mansoni), and the skin granuloma model was established by subcutaneous inoculation of the isolated hepatic granulomas. NK cell activity in lymph nodes and spleen, measured by 51Cr-release assay against YAC-1 cells, was compared to that in age-matched control mice. The activity decreased progressively as granulomas developed without changing the number of NK-1.1+ cells. The reduced NK cell activity was not reversed by administration of indomethacin. In order to further substantiate whether NK cells contribute to granulomatous inflammation, NK cells were depleted in the mice by injection of anti-NK-1.1 mAb. Reduction of NK cell activity (70-90%) was achieved during granuloma formation. An increase of about 20% in the mean granuloma diameter was detected in the mAb-treated mice in both models. Moreover, the percentage of granuloma takes in the skin model was enhanced (65% increase). The mAb treatment did not alter T cell counts in granulomas, T cell subset numbers or proliferative response in spleen. These findings indicate that NK cells directly play a regulatory role in granulomatous inflammation.

Animals↗