Elevated expression of beta 1 and beta 2 integrins, intercellular adhesion molecule 1, and endothelial leukocyte adhesion molecule 1 in the skin of patients with systemic sclerosis of recent onset.
OBJECTIVE
To investigate the possible role of integrins and cell adhesion molecules in the pathogenesis of the mononuclear cell infiltration and fibrosis of skin that occurs in systemic sclerosis (SSc).


METHODS
The presence and topographic distribution of beta 1, beta 2, and beta 4 integrins, as well as of endothelial leukocyte adhesion molecule 1 (ELAM-1) and intercellular adhesion molecule 1 (ICAM-1), was examined immunohistochemically in affected skin from 8 patients with rapidly progressive SSc of recent onset. The expression of the beta 1 integrin gene was also investigated by in situ hybridization with a human sequence-specific complementary DNA.


RESULTS
The presence of beta 1 integrin epitopes and the corresponding messenger RNA within inflammatory cells surrounding small vessels was demonstrated in SSc skin but not in normal skin. Lymphocytes positive for beta 2 integrin were also found only in SSc skin, and they appeared in close proximity to small blood vessels and collagen bundles. Immunostaining for beta 4 integrin epitopes revealed no differences between normal and SSc skin. ELAM-1 and ICAM-1 monoclonal antibodies, which identify epitopes indicative of endothelial cell activation, stained endothelial cells in SSc skin but not normal skin.


CONCLUSIONS
These observations suggest that the complex interactions of beta 1 and beta 2 integrins, as well as ELAM-1 and ICAM-1, may be intimately involved in the pathogenesis of SSc, perhaps by mediating the homing and targeting of pathogenetic lymphocytes to the affected tissues.
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
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S
Sollberg
J
J
Peltonen
J
J
Uitto
S A
SA
Jimenez
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000276:immunology; D004247:DNA / Q000032:analysis; D019040:E-Selectin; D000939:Epitopes / Q000032:analysis; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1; D046911:Macromolecular Substances; D009693:Nucleic Acid Hybridization; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012867:Skin / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D000939:Epitopes; D016023:Integrins; D046911:Macromolecular Substances; D018799:Intercellular Adhesion Molecule-1; D004247:DNA