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(Journal of Leukocyte Biology. 2001;69:605-612.)
© 2001 by Society for Leukocyte Biology

CD38 expression and functional activities are up-regulated by IFN- on human monocytes and monocytic cell lines

Tiziana Musso^*, Silvia Deaglio, Luisa Franco^,,||, Liliana Calosso, Raffaele Badolato^#, Giovanni Garbarino^**, Umberto Dianzani and Fabio Malavasi

^* Department of Public Health and Microbiology,
Laboratory of Cell Biology, Department of Genetics, Biology and Biochemistry, and
^** Institute of Internal Medicine, University of Turin, Turin, Italy;
Biocrystallography Center CNR, University Federico II, Naples, Italy;
Institute G. Gaslini, Genoa, Italy;
^|| Department of Biochemistry, University of Genoa, Genoa, Italy;
^# Department of Pediatrics, University of Brescia, Brescia, Italy; and
Department of Medical Science, A. Avogadro University of Eastern Piedmont, Novara, Italy

Correspondence: Tiziana Musso, Ph.D., Department of Public Health and Microbiology, University of Turin, via Santena, 9, 10126 Torino, Italy. E-mail: musso{at}molinette.unito.it

Human CD38, a surface molecule expressed by immature and activated T and B lymphocytes, has been characterized as a molecule transducing activation and proliferation signals, and intervening in adhesion to endothelium via its ligand CD31. CD38 is also a complex ectoenzyme featuring ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities, leading to the synthesis and degradation of cADPR, a Ca⁺-mobilizing agent. We investigated the effects of monocyte-activating stimuli (IFN-, IL-2, LPS, TNF-, and GM-CSF) on the expression and function of CD38, starting from the observation that human monocytes and the derived lines U937, THP-1, and Mono-Mac-6 bear the molecule on their surface. Our results indicate that IFN- is a strong up-modulator of CD38, and IL-2 increases its expression only modestly. LPS, TNF-, and GM-CSF had no detectable effects. Treatment with IFN- produced a dose- and time-dependent up-regulation of CD38 in monocytes and monocytic lines, which was paralleled by increased ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase activities. Furthermore, CD38 ligation by specific MoAb reduced the IFN--dependent enhancement of monocyte-dynamic adhesion to endothelial monolayers. These findings identify IFN- as a modulator of monocytic CD38 expression and indicate that CD38 plays a specific role in the activation and adhesion processes performed by monocytes.

Key Words: cytokines • ADP-ribosyl cyclase • cADPR hydropase

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