scholarly journals Distinct functions for integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4/bullous pemphigoid antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes.

1990 ◽  
Vol 111 (6) ◽  
pp. 3141-3154 ◽  
Author(s):  
W G Carter ◽  
P Kaur ◽  
S G Gil ◽  
P J Gahr ◽  
E A Wayner
Keyword(s):  
Bullous Pemphigoid ◽  
Dominant Role ◽  
Focal Adhesions ◽  
Human Keratinocytes ◽  
Isolation Procedure ◽  
Basement Membrane Zone ◽  
Basal Cells ◽  
Bullous Pemphigoid Antigen ◽  
Insoluble Complex ◽  
Affinity Isolation

Basal cells of stratified epidermis are anchored to the basement membrane zone (BMZ) of skin via hemidesmosomes. We previously identified integrin alpha 3 beta 1, in focal adhesions (FAs), of cultured human keratinocytes (HFKs) as a mediator of HFK adhesion to secreted BMZ-like extracellular matrix (ECM; Carter, W.G., E.A. Wayner, T.S. Bouchard, and P. Kaur. 1990. J. Cell Biol. 110: 1387-1404). Here, we have examined the relation of integrins alpha 6 beta 4 and alpha 3 beta 1, to bullous pemphigoid antigen (BPA), a component of hemidesmosomes. We conclude that alpha 6 beta 4 in HFKs localizes in a new stable anchoring contact (SAC) that cooperates with alpha 3 beta 1-FAs to mediate adhesion to ECM, based on the following. (a) Comparison of secreted ECM, with exogenous laminin, fibronectin and collagen identified ECM as the preferred ligand for HFK adhesion and spreading and for formation of both alpha 6 beta 4-SACs and alpha 3 beta 1-FAs. (b) Inhibition of HFK adhesion with combined anti-alpha 3 beta 1 (P1B5) and anti-alpha 6 beta 4 (GoH3) antibodies indicated that both receptors were functional in adhesion to ECM while alpha 3 beta 1 played a dominant role in spreading. (c) alpha 6 beta 4 colocalized with BPA in SACs that were proximal to but excluded from FAs. Both alpha 6 beta 4-SACs and alpha 3 beta 1-FAs were in contact with the adhesion surface as indicated by antibody exclusion and interference reflection microscopy. (d) In contrast to alpha 3 beta 1-FAs, alpha 6 beta 4-SACs were present only in nonmotile cells, not associated with stress fibers, and were relatively stable to detergents and urea, suggesting a nonmotile, or anchoring function for SACs and motility functions for alpha 3 beta 1-FAs. (e) alpha 6 beta 4 formed a detergent-insoluble complex with exogenous ECM in an affinity isolation procedure, confirming the ability of an unidentified ECM ligand to interact with alpha 6 beta 4. (f) We suggest that alpha 6 beta 4/BPA-SACs in culture restrict migration of HFKs on ECM while alpha 3 beta 1-FAs form dynamic adhesions in spreading and migrating cells. alpha 6 beta 4/BPA-SACs in culture bear functional and compositional similarities to hemidesmosomes in skin.

Activation of human keratinocyte migration on type I collagen and fibronectin

1990 ◽  
Vol 96 (2) ◽  
pp. 197-205
Author(s):  
M. Guo ◽  
K. Toda ◽  
F. Grinnell
Keyword(s):  
Type I Collagen ◽  
Cultured Cells ◽  
Focal Adhesions ◽  
Human Keratinocytes ◽  
Type I ◽  
Integrin Subunit ◽  
Basal Cells ◽  
Keratinocyte Migration ◽  
Beta 1 Integrin ◽  
Cells Cultured

The purpose of our studies was to learn more about the regulation of keratinocyte migration. Human keratinocytes freshly harvested from skin were relatively immotile cells, whereas keratinocytes harvested from cell culture migrated on type I collagen or fibronectin as measured in a phagokinesis assay. Development of migratory competence by keratinocytes varied depending on the culture substratum. Cells cultured on plastic were activated more quickly and to a greater extent than cells cultured on dermis. The effect of the culture substratum on migratory competence was reversible. That is, cells cultured on plastic showed reduced activity after subculture on dermis. Cells cultured on dermis showed increased activity after subculture on plastic. Freshly isolated as well as cultured keratinocytes contained beta 1 integrin subunits, but only cultured cells were able to organize the subunits into focal adhesions. These adhesion sites also contained vinculin. In epidermal explants, beta 1 integrin subunits were mostly in basal cells, often more prominent between lateral cell borders than at the epidermal-dermal interface. In keratinocytes that migrated out of skin explants, there appeared to be an increase in the intensity of beta 1 integrin subunit immunostaining, possibly because of the change in shape of migrating cells. Also, beta 1 integrin subunits were found around and beneath migrating keratinocytes. These results show that changes in the distribution of beta 1 integrin subunits accompany development of migratory competence.

Localisation of bullous pemphigoid antigen 180 (BP180) in cultured human keratinocytes: functionally relevant modification by calcium

2006 ◽  
Vol 298 (6) ◽  
pp. 283-290 ◽  
Author(s):  
Enno Schmidt ◽  
Barbara Wehr ◽  
Katharina Wolf ◽  
Cassian Sitaru ◽  
Eva -B. Bröcker ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Human Keratinocytes ◽  
Bullous Pemphigoid Antigen

scholarly journals Localization of Bullous Pemphigoid Antigen (BPA) in Isolated Human Keratinocytes

1985 ◽  
Vol 85 (3) ◽  
pp. 187-190 ◽  
Author(s):  
Marcelle Regnier ◽  
Pierre Vaigot ◽  
Serge Michel ◽  
Michel Prunieras
Keyword(s):  
Bullous Pemphigoid ◽  
Human Keratinocytes ◽  
Bullous Pemphigoid Antigen

Mustard-gas skin lesion and bullous pemphigoid antigen

1994 ◽  
Vol 52 ◽  
pp. 254-255
Author(s):  
John P. Petrali ◽  
Susan B. Oglesby ◽  
Tracey A. Hamilton
Keyword(s):  
Bullous Pemphigoid ◽  
Sulfur Mustard ◽  
Repair Process ◽  
Chemical Warfare Agent ◽  
Mustard Gas ◽  
Basal Cells ◽  
Immunochemical Study ◽  
Bullous Pemphigoid Antigen ◽  
Type Iv ◽  
Bullous Diseases

Human dermal exposure to the chemical warfare agent, sulfur mustard gas (HD), results in the delayed formation of fluid filled bullae which are incapacitating, persistent and slow to heal. In animal investigations, the pathology is typically described as that occurring during a prevesication period and that of a vesication period. During the first 24 hours, the pathology involves the latent lethal targeting of epidermal basal cells, a disabling of hemidesmosomes (prevesication) and a progressive inflammatory edema of the lamina lucida all contributing to the formation of characteristic lucidolytic microvesicles persisting at the dermal epidermal junction (vesication). We are now investigating possible primary or secondary HD-induced effects on extracellular adherent structural proteins of the basement membrane microenvironment which may contribute to vesication or may influence the repair process. Proteins selected for immunochemical study were laminin, type IV collagen, bullous pemphigoid antigen (BPA), fibronectin and desmosomal protein.Effects on BPA were of special interest. Its epitopes, BPA1 and BPA2, have been anatomically localized to basal cell hemidesmosomes and lamina lucida, and its role as an autoimmune antigen in the etiology of clinical bullous diseases such as bullous pemphigoid is well documented.

Cloning of Partial cDNA for Mouse 180-kDa Bullous Pemphigoid Antigen (BPAG2), a Highly Conserved Collagenous Protein of the Cutaneous Basement Membrane Zone

1992 ◽  
Vol 99 (3) ◽  
pp. 258-263 ◽  
Author(s):  
Kehua. Li ◽  
George J Giudice ◽  
Katsuto. Tamai ◽  
Haeyoung. Choi Do ◽  
Daisuke. Sawamura ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Bullous Pemphigoid ◽  
Basement Membrane Zone ◽  
Bullous Pemphigoid Antigen ◽  
Partial Cdna

scholarly journals Degradation of the epidermal-dermal junction by proteolytic enzymes from human skin and human polymorphonuclear leukocytes.

1984 ◽  
Vol 160 (4) ◽  
pp. 1027-1042 ◽  
Author(s):  
R A Briggaman ◽  
N M Schechter ◽  
J Fraki ◽  
G S Lazarus
Keyword(s):  
Human Skin ◽  
Bullous Pemphigoid ◽  
Polymorphonuclear Leukocytes ◽  
Skin Diseases ◽  
Proteolytic Enzymes ◽  
Cathepsin G ◽  
Basal Cells ◽  
Lamina Densa ◽  
Normal Human Skin ◽  
Bullous Pemphigoid Antigen

The degradation of normal human skin by the human polymorphonuclear leukocyte proteinases cathepsin G and elastase, and by a human skin chymotrypsin-like proteinase that appears to be a mast cell constituent, was examined. Enzymes were incubated with fresh, split-thickness skin for up to 8 h; the tissue was examined ultrastructurally and immunohistochemically using antibodies to known basement membrane constituents. In all cases, the primary damage observed was at the epidermal-dermal junction. Elastase degraded the lamina densa leaving scattered and disorganized anchoring fibrils, dermal microfibril bundles, and normal-appearing collagen fibers. Immunohistochemically, type IV collagen, laminin, KF1 antigen, and EBA antigen were absent. The bullous pemphigoid antigen was present and localized on the basal cells. Epidermal-dermal separation produced by the chymotrypsin-like proteinases, cathepsin G, and the human skin proteinase, was confined to the lamina lucida. The lamina densa and sub-lamina densa fibrillar network remained intact. The human skin chymotrypsin-like proteinase produced extensive epidermal-dermal separation, while cathepsin G, at comparable concentrations, produced only focal separations. Immunohistochemically, all antigens were present after incubation with enzyme. The bullous pemphigoid antigen, however, was found on the epidermal side of the split, while laminin was found on the dermal side. These results show that the epidermal-dermal junction is highly susceptible to neutral serine proteinases located in mast cells and polymorphonuclear leukocytes. Although all the proteinases produce epidermal-dermal separation, the patterns and extent of degradation are different. The distinctive patterns of degradation may provide a clue to the involvement of these proteinases in skin diseases.

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