Role of intracellular Ca2+ levels in the regulation of CD11a/CD18 mediated cell adhesion.
CD2, CD3, and MHC class II have been demonstrated to stimulate lymphocyte function-associated antigen (LFA)-1 (CD11a/CD18) mediated adhesion (Van Kooyk et al., 1989, Dustin and Springer, 1989; Mourad et al., 1990). Activation of LFA-1 may be mediated by different intracellular signals generated from these stimuli, since previous findings suggest that triggering of LFA-1 through CD2 or CD3 leads to sustained and transient cell adhesion respectively (Van Kooyk et al., 1989). We investigated the role of intracellular signalling pathways in more detail. The results demonstrate that, in addition to protein tyrosine kinase (PTK) and protein kinase C (PKC) mediated signalling, increase in cytosolic-free calcium ([Ca2+]i) levels play a major role in the activation of LFA-1. The calcium ionophore Ionomycin, which increases [Ca2+]i is capable of directly activating LFA-1. Furthermore, activation of LFA-1 by triggering through CD2, CD3 or MHC class II is associated with an increase in [Ca2+]i levels, with kinetics that directly correlate with cell adhesiveness. Moreover, entry of extracellular Ca2+ via Ca-channels is involved in both the CD3- and MHC class II, as well as part of the CD2 induced LFA-1 activation. Depletion of intracellular calcium results in unresponsiveness of LFA-1 to these stimuli, further demonstrating a regulatory role for [Ca2+]i in LFA-1 mediated adhesion.
van Kooyk
Y
Y
Division of Immunology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam.
Weder
P
P
Heije
K
K
de Waal Malefijt
R
R
Figdor
C G
CG
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018821:CD18 Antigens; D018801:CD2 Antigens; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007739:L Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D017455:Receptors, IgE / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018821:CD18 Antigens; D018801:CD2 Antigens; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D018799:Intercellular Adhesion Molecule-1; D008274:Magnesium; D002118:Calcium