CD166 expression, characterization, and localization in salivary epithelium: implications for function during sialoadenitis.
CD166 is an Ig superfamily molecule that binds homotypically to itself and heterotypically to CD6. Interactions between CD6 and CD166 are important during immune development and in alloreactivity. CD166 is expressed at increased levels in selected cancers and in rheumatoid arthritis synovium. Knowledge that CD166 was expressed in normal human salivary epithelium led to these studies of CD166 and CD6 in diseased mouse salivary glands, that resemble pathology seen in the human disease, Sjögren's syndrome. We showed that in mouse salivary epithelium CD166 was expressed but that expression of CD166 did not necessarily predict its function. Recombinant soluble CD6-Ig bound to CD6 ligands (CD6L) on transformed and freshly isolated salivary epithelial cells. Cross-blocking studies showed that binding of CD6-Ig to salivary epithelium was in part dependent on CD166, but that CD6-Ig binding may also involve additional CD6L. Binding of CD6-Ig was sensitive to trypsin digestion but resistant to digestion by collagenase and sialidase. Anti-CD166 ab precipitated CD166 from salivary epithelium pre- and post-treatment with the pro-inflammatory cytokine IFN-gamma. In contrast CD6-Ig only precipitated CD166 from IFN-gamma treated cells. More extensive colocalization between CD166 and the actin cytoskeleton was observed in sialoadenitis epithelium compared to control. We conclude that during sialoadenitis, CD166 undergoes a gain of function, resulting in closer association with the actin cytoskeleton and increased capacity to bind CD6. We suggest that altered CD166 function may contribute to the pro-inflammatory milieu during sialoadenitis seen in Sjögren's syndrome.
Abidi
Syed M A
SM
Department of Pediatrics, CASE School of Medicine and Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, USA.
Saifullah
Mohammad K
MK
Zafiropulos
Marie D
MD
Kaput
Cara
C
Bowen
Michael A
MA
Cotton
Calvin
C
Singer
Nora G
NG
D000199:Actins / Q000378:metabolism; D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D017364:Collagenases / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D000939:Epitopes / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D011485:Protein Binding / Q000187:drug effects; D012469:Salivary Glands / Q000378:metabolism*; D012793:Sialadenitis / Q000378:metabolism*; D014357:Trypsin / Q000502:physiology; D014393:Tuberculosis, Oral
D000199:Actins; D020410:Activated-Leukocyte Cell Adhesion Molecule; D000939:Epitopes; D007371:Interferon-gamma; D014357:Trypsin; D017364:Collagenases