SPECIFIC-INHIBITION OF LYMPHOCYTE-PROLIFERATION AND INDUCTION OF APOPTOSIS BY CLL-I, A BETA-GALACTOSIDE-BINDING LECTIN

beta-Galactoside-binding lectins or galectins are a family of closely related carbohydrate-binding proteins which functions still remain to be elucidated, Several evidence suggest they could play a role in diff erent biological processes, such as cell growth regulation and immunom odulation, In the present study we report that affinity-purified CLL-I (chicken lactose lectin-I), an acidic 16-kDa galectin exhibits specif ic growth regulatory properties, Con A-stimulated rat spleen mononucle ar cells showed a marked dose-dependent growth inhibition upon incubat ion with the galectin protein, Cell growth arrest was highly prevented by galectin-specific sugars, In addition, biochemical, cytofluorometr ical, and morphological evidence are also provided to show that these inhibitory properties are related to a positive control in the apoptot ic threshold of spleen mononuclear cells, Flow cytometric analysis sho wed a dose- and time-dependent increase of cells with hypodiploid DNA content upon exposure to CLL-I, Moreover, cells treated with CLL-I dis played the typical ultrastructural changes compatible with apoptosis, mainly chromatin condensation and margination along the inner surface of the nuclear envelope, Finally, the highly characteristic ''ladder'' pattern of DNA fragmentation into oligonucleosome-length fragments of similar to 180-200 bp could be found within 6 h of cell culture with CLL-I, mainly in the T cell-enriched population, Induction of apoptosi s by a beta-galactoside-binding protein highlights a potentially novel mechanism for regulating the immune response and points to a rational basis for the postulated immunomodulatory properties of this protein family.