PubMed · 4247927
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
U W Schnyder. 1970. Inherited ichthyoses.. https://pubmed.ncbi.nlm.nih.gov/4247927/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
The autoimmune blistering skin diseases pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are mainly caused by autoantibodies against desmosomal cadherins. In this study, we provide evidence that PV-immunoglobulin G (IgG) and PF-IgG induce skin blistering by interference with Rho A signaling. In vitro, pemphigus IgG caused typical hallmarks of pemphigus pathogenesis such as epidermal blistering in human skin, cell dissociation, and loss of desmoglein 1 (Dsg 1)-mediated binding probed by laser tweezers. These changes were accompanied by interference with Rho A activation and reduction of Rho A activity. Pemphigus IgG-triggered keratinocyte dissociation and Rho A inactivation were p38 mitogen-activated protein kinase dependent. Specific activation of Rho A by cytotoxic necrotizing factor-y abolished all pemphigus-triggered effects, including keratin retraction and release of Dsg 3 from the cytoskeleton. These data demonstrate that Rho A is involved in the regulation of desmosomal adhesion, at least in part by maintaining the cytoskeletal anchorage of desmosomal proteins. This may open the possibility of pemphigus treatment with the epidermal application of Rho A agonists.
Explore the source record for details and available documents.
Shedding of adhesion molecules has been described for members of the selectin and immunoglobulin superfamilies, but integrins are not known to be shed. Here, we describe shedding of the integrin lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) from human leukocytes during the cutaneous inflammatory response to the blistering agent cantharidin. Expression of LFA-1 was significantly diminished on blister-infiltrated neutrophils (P < .001) and monocytes (P = .02) compared with cells in peripheral blood, but expression on lymphocytes remained unchanged. A capture enzyme-linked immunosorbent assay (ELISA) indicated that LFA-1 was shed into blister fluid as a heterodimer expressing an intact headpiece with I and I-like epitopes. However, a CD11a central region epitope, G25.2, was absent and this remained expressed as a "stub" on the cell surface of blister neutrophils. Western analysis of soluble LFA-1 revealed a truncated 110-kDa CD11a chain and a minimally truncated 86-kDa CD18 chain. However, LFA-1 was shed in a ligand-binding conformation, since it expressed KIM-127 and 24 activation epitopes and bound to solid-phase ICAM-1. Shed LFA-1 was also detected in a synovial effusion by ELISA and Western analysis. We hypothesize that LFA-1 shedding may play a role in leukocyte detachment after transendothelial migration and in regulating integrin-dependent outside-in signaling.