Thalidomide derivatives and the immune system. 6. Effects of two derivatives with no obvious teratogenic potency on the pattern of integrins and other surface receptors on blood cells of marmosets.
The two thalidomide (Thd) derivatives beta-EM12 and phthalimidophthalimide (Phtpht), which exhibit no obvious teratogenicity, were tested for their ability to induce changes in the pattern of lymphocyte subpopulations, and especially changes in integrin receptors, in marmosets (Callithrix jacchus). Previously, Thd and its highly teratogenic derivative alpha-EM12 had been found to alter the expression of adhesion molecules, such as CD2 (LFA-2) or CD11a/CD18 (LFA-1). None of these typical effects on adhesion receptors were observed following administration of the relatively high daily doses of 50 mg/kg body wt beta-EM12 and Phtpht. Nevertheless, there were some minor effects, such as alterations in the receptor density on peripheral blood mononuclear cells, which were often contrary to the effects induced by Thd. Mainly affected were: CD8 cells, B cells bearing the CD54 receptor and CD4 cells bearing the CD56 (NCAM) surface marker. We observed an increase in the receptor density of CD11c (p150,95) on monocytes with Phtpht but not with beta-EM12. The inability of the two substances with no obvious teratogenic potential to typically modify beta 2-integrin receptors on white blood cells at comparatively high doses is consistent with our hypothesis, that the teratogenicity of Thd may also be linked to alterations in the expression of adhesion molecules.
Nogueira
A C
AC
University Medical Center, Free University Berlin, Germany.
Neubert
R
R
Felies
A
A
Jacob-Müller
U
U
Frankus
E
E
Neubert
D
D
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002144:Callithrix; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005434:Flow Cytometry; D007107:Immune System; D016023:Integrins / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000187:drug effects; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D019038:Platelet Glycoprotein GPIb-IX Complex; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013723:Teratogens / Q000633:toxicity*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000633:toxicity
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016023:Integrins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D011956:Receptors, Cell Surface; D013723:Teratogens; C094990:adhesion receptor; C060329:EM 16; C088185:phthalimidophthalimide; D013792:Thalidomide