Junctional adhesion molecule-A is abnormally expressed in diffuse cutaneous systemic sclerosis skin and mediates myeloid cell adhesion.
OBJECTIVE
To investigate the role of junctional adhesion molecule-A (JAM-A) in the pathogenesis of systemic sclerosis (SSc).


METHODS
Biopsy specimens from proximal and distal arm skin and serum were obtained from patients with SSc and normal volunteers. To determine the expression of JAM-A on SSc dermal fibroblasts and in SSc skin, cell surface ELISAs and immunohistology were performed. An ELISA was designed to determine the amount of soluble JAM-A (sJAM-A) in serum. Myeloid U937 cell-SSc dermal fibroblast and skin adhesion assays were performed to determine the role of JAM-A in myeloid cell adhesion.


RESULTS
The stratum granulosum and dermal endothelial cells (ECs) from distal arm SSc skin exhibited significantly decreased expression of JAM-A in comparison with normal volunteers. However, sJAM-A was increased in the serum of patients with SSc compared with normal volunteers. Conversely, JAM-A was increased on the surface of SSc compared with normal dermal fibroblasts. JAM-A accounted for a significant portion of U937 binding to SSc dermal fibroblasts. In addition, JAM-A contributed to U937 adhesion to both distal and proximal SSc skin.


CONCLUSIONS
JAM-A expression is dysregulated in SSc skin. Decreased expression of JAM-A on SSc ECs may result in a reduced response to proangiogenic basic fibroblast growth factor. Increased JAM-A expression on SSc fibroblasts may serve to retain myeloid cells, which in turn secrete angiogenic factors.
Hou
Y
Y
University of Michigan Medical School, Department of Internal Medicine, Ann Arbor, MI 48109-2200, USA.
Rabquer
B J
BJ
Gerber
M L
ML
Del Galdo
F
F
Jimenez
S A
SA
Haines
G K
GK
Barr
W G
WG
Massa
M C
MC
Seibold
J R
JR
Koch
A E
AE
D000328:Adult; D001132:Arm / Q000098:blood supply; D001808:Blood Vessels / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000502:physiology*; D011956:Receptors, Cell Surface; D045743:Scleroderma, Diffuse / Q000378:metabolism*; D012867:Skin / Q000098:blood supply / Q000378:metabolism*; D020298:U937 Cells
D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D007136:Immunoglobulins; D011956:Receptors, Cell Surface