Biomedical subjects

C Le Poole

Publications and source records attributed to C Le Poole.

3 recordsLinked to original sources

PubMed2001

Molecular and functional characterization of sodium--hydrogen exchanger in skin as well as cultured keratinocytes and melanocytes.

The sodium--hydrogen (Na(+)/H(+)) exchanger is one of the few transporter proteins involved in the regulation and maintenance of intracellular pH and cell volume in most eukaryotic cell types. The current study investigates the expression of isoforms of the Na(+)/H(+) exchanger (NHE) in human skin and in cultured keratinocytes, melanocytes, and melanoma cells by reverse transcription-polymerase chain reaction (RT--PCR), immunohistochemical analysis and functional studies. Neonatal foreskins were used to isolate RNA from epidermis and dermis, and to initiate cultures of keratinocytes and melanocytes. RT--PCR on RNA isolated from epidermis, dermis, keratinocytes, melanocytes and melanoma cells using PCR primers specific for NHE-1 yielded a 463 bp PCR product. RT--PCR performed using primers specific for NHE isoforms 2, 3, 4 and 5 did not yield any products. Western blotting analysis (of keratinocyte and melanocyte cell cultures) and indirect immunohistochemistry on neonatal foreskin, keratinocytes, melanocytes and melanoma cells using a NHE-1-specific polyclonal antibody demonstrated NHE-1 expression at the protein level. Physiological regulation of intracellular pH using a pH-sensitive dye, BCECF, detected an amiloride-sensitive NHE activity in human keratinocyte, melanocyte and melanoma cell cultures. These results indicate that cultures of human keratinocytes and melanocytes established from human skin and melanoma cells express the NHE-1 isoform of the sodium--hydrogen exchanger.

Cells, Cultured↗

PubMed2000

Local immune response in skin of generalized vitiligo patients. Destruction of melanocytes is associated with the prominent presence of CLA+ T cells at the perilesional site.

In situ immune infiltrates in lesional, perilesional, and nonlesional skin biopsies from patients with vitiligo were analyzed by immunohistochemistry and compared with immune infiltrates found in the skin of normal healthy donors and relevant disease controls. An increased influx of activated skin-homing T cells and macrophages were seen in the perilesional biopsies. The overall percentages of cutaneous leukocyte-associated antigen-positive (CLA+) T cells were similar to those found in normal healthy donors. This is compatible with the similar expression of E-selectin. Most strikingly, however, the CLA+ T cells in perilesional skin were mainly clustered in the vicinity of disappearing melanocytes, and 60% to 66% of these interacting T cells expressed perforin and granzyme-B. The perforin+/granzyme-B+ cells were not seen in locations different from that of disappearing melanocytes. Interestingly, the majority of the infiltrating T cells were HLA-DR/CD8+. Another hallmark of the present study is the focal expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR in the epidermis at the site of interaction between the immune infiltrates and the disappearing melanocytes. The data presented in this study are consistent with a major role for skin-homing T cells in the death of melanocytes seen in vitiligo.

Adult↗

PubMed1997

Vitiligo.

Vitiligo involves a progressive loss of melanocytes from the epidermis and hair follicles. Milky-white patches appear resulting in cosmetic disfiguration that is most apparent in dark-skinned individuals. The disease is further classified according to distribution pattern and extent of depigmentation. The presence of several clinical subtypes may reflect the diversity in causative factors. To select appropriate therapeutic measures it is important to distinguish vitiligo from other disorders that affect melanocyte function. Although vitiligo has a characteristic clinical appearance and histological features, the presence of early or atypical lesions often requires the exclusion of other disorders such as postinflammatory hypopigmentation and piebaldism. Multiple hypotheses have been put forward to explain vitiligo. An inherited tendency to develop depigmentation may involve the inherent aberrancies that have been observed in nonlesional vitiligo melanocytes in vivo as well as in vitro. These abnormalities potentially render vitiliginous melanocytes more vulnerable to assaults from extracellular factors. Such factors include keratinocyte physiology, extracellular matrix composition, humoral and cellular immunity, and environmental agents. Therapies aimed at repopulation of lesional skin include phototherapy, application of topical corticosteroids, and transplantation of skin or skin cells. Moreover, micropigmentation or camouflage can be used to restore a pigmented appearance to lesional skin. In patients in which vitiligo affects extensive areas of the body, depigmentation may be the treatment of choice. In all, this acquired pigmentary disorder can be treated in a variety of ways and should not be regarded as an untreatable affliction.

Administration, Cutaneous↗