{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:48:46Z","timestamp":1770720526507,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,12,6]],"date-time":"2005-12-06T00:00:00Z","timestamp":1133827200000},"content-version":"vor","delay-in-days":3506,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1996,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The effect of the guanosine triphosphate\u2010binding protein (G\u2010protein) inhibitors cholera toxin (Ctx) and pertussis toxin (Ptx) has been analyzed on lymphocyte function\u2010associated antigen 1 (LFA\u20101)\u2010dependent adhesion and signal transduction in human natural killer (NK) cells. Ctx, but not Ptx, inhibited the LFA\u20101\u2010dependent adhesion of NK cells to tumor target cells which constitutively express the intercellular cell adhesion molecule\u20101 (ICAM\u20101) and to NIH\/3T3 mouse fibroblasts stably transfected with human ICAM\u20101. This effect was detectable only by the use of the entire Ctx but not of the Ctx B subunit. In addition, Ctx could inhibit both NK cell binding and spreading to purified ICAM\u20101 protein. NK cell treatment with Ctx modified neither the surface expression of LFA\u20101 nor its Mg<jats:sup>2+<\/jats:sup> binding site. These findings, together with the absence of any detectable effect of Ctx on the constitutive phosphorylation of LFA\u20101\u03b1, suggests that this toxin modifies the avidity of LFA\u20101 for ICAM\u20101 by acting on LFA\u20101\u2010cytoskeletal protein association. Unlike Ctx, Ptx did not affect NK cell adhesion. The effects of Ctx and Ptx are unlikely to depend on intracellular levels of cyclic adenosine 3\u2032,5\u2032\u2010monophosphate (cAMP), since a strong increase of cAMP was induced by both toxins. Moreover, this was confirmed by the observation that the LFA\u20101\u2010dependent adhesion was not inhibited by the adenylate cyclase activator forskolin (FSK), the phosphodiesterase inhibitor isobutyl\u20101\u2010methylxantine (IBMX), or both, which increase intracellular cAMP levels. Unlike the differential effect on cell adhesion, both the intracellular calcium [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> increase and phosphoinositide breakdown mediated via LFA\u20101 were consistently inhibited in a dose\u2010dependent manner by both Ctx and Ptx. Also in this case, the inhibitory effect did not depend on an increase of intracellular cAMP as indicated by NK cell treatment with FSK, IBMX, or both. Further evidence of the involvement of G\u2010proteins in LFA\u20101\u2010mediated signal transduction was the inhibitory effect of the GDP analog guanosine\u20105\u2032\u2010O\u20102\u2010thiodiphosphate (GDP\u00dfS) on LFA\u20101\u2010mediated calcium mobilization. Taken together, our data provide evidence that the LFA\u20101\u2010mediated NK cell adhesion and signal transduction are partially independent phenomena which may be regulated by different G\u2010proteins.<\/jats:p>","DOI":"10.1002\/eji.1830260502","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T02:03:19Z","timestamp":1172800999000},"page":"967-975","source":"Crossref","is-referenced-by-count":14,"title":["Dissection of lymphocyte function\u2010associated antigen 1\u2010dependent adhesion and signal transduction in human natural killer cells shown by the use of cholera or pertussis toxin"],"prefix":"10.1002","volume":"26","author":[{"given":"Alessandro","family":"Poggi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franca","family":"Spada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Tomasello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentino","family":"Revello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Pella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Raffaella","family":"Zocchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Moretta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.158.6.1785"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.05.040187.001255"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/346425a0"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.4049\/jimmunol.143.10.3157","volume":"143","author":"Pardi R.","year":"1989","journal-title":"J. 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