Platelet-endothelial cell adhesion molecule-1 and CD146: soluble levels and in situ expression of cellular adhesion molecules implicated in the cohesion of endothelial cells in idiopathic inflammatory myopathies.
OBJECTIVE
Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases characterized by chronic inflammation of muscles. We investigated the role of cellular adhesion molecules implicated in the cohesion of endothelial cells in IIM.


METHODS
In 22 patients with IIM we investigated plasma concentrations of soluble junctional adhesion molecules [platelet-endothelial cell adhesion molecule (sPECAM-1) and sCD146] and cellular adhesion molecules [sP-selectin, sE-selectin, intercellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1)] implicated in leukocyte/endothelial cell interactions. Results were compared to a control group. Muscle biopsy samples from 8 out of 22 IIM patients were studied by immunohistochemistry for tissue expression of these molecules and compared to normal muscle samples. PECAM-1 and CD146 expression was also studied using immunoblots from muscle biopsies from 5 patients and 2 controls.


RESULTS
We observed distinct patterns of soluble levels and in situ expression between dermatomyositis (DM), polymyositis (PM), and sporadic inclusion body myositis (s-IBM). PM samples showed significantly increased levels of sCD146, sPECAM-1, and s-ICAM1 and increased expression of CD146, CD31, and ICAM-1 in endothelial cells, whereas CD146 and ICAM-1 were also recorded in some muscle fibers. In DM, sE-selectin, sP-selectin, and sPECAM-1 were significantly increased, with abnormal expression of ICAM-1 in endothelial cells and perifascicular muscle fibers. In the small group of s-IBM samples, results were similar to PM, but the only significant increase was the level of sPECAM-1. Immunoblots confirmed increased expression of PECAM-1 and CD146 in all IIM muscles in comparison to controls, with the highest expression in PM and IBM samples.


CONCLUSIONS
We observed abnormal increases of soluble levels of adhesion molecules implicated in endothelial cell junctions in PM (sCD146, sPECAM-1) and to a lesser extent in DM and s-IBM (sPECAM-1). We conclude that the distinctly different profiles between PM/s-IBM and DM reflect differences in the pathophysiological background of these diseases.
Figarella-Branger
Dominique
D
Laboratoire de Biopathologie de l'Adhésion et de la Signalisation, EA 3281, Faculté de Médecine Timone, Université de la Méditerranée, Marseille, France. Dominique.Figarella-Branger@medecine.univ-mrs.fr
Schleinitz
Nicolas
N
Boutière-Albanèse
Brigitte
B
Camoin
Laurence
L
Bardin
Nathalie
N
Guis
Sandrine
S
Pouget
Jean
J
Cognet
Céline
C
Pellissier
Jean-François
JF
Dignat-George
Françoise
F
D051929:CD146 Antigen / Q000097:blood*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000097:blood*; D003882:Dermatomyositis / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D019040:E-Selectin / Q000097:blood; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009220:Myositis / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D018979:Myositis, Inclusion Body / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D019007:P-Selectin / Q000097:blood; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood*; D017285:Polymyositis / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D051929:CD146 Antigen; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1