The functional interactions between CD98, beta 1-integrins, and CD147 in the induction of U937 homotypic aggregation

CD98 is expressed on both hematopoietic and nonhematopoietic cells and has been implicated in a variety of different aspects of cell physiology and im munobiology. In this study, the functional interactions between CD98 and ot her adhesion molecules on the surface of the promonocyte line U937 are exam ined by means of a quantitative assay of cell aggregation. Several of the C D98 antibodies induced homotypic aggregation of these cells without affecti ng cellular viability or growth. Aggregation induced by CD98 antibodies cou ld he distinguished from that induced by beta1-integrin (CD29) ligation by lack of sensitivity to EDTA and by increased sensitivity to deoxyglucose, A ggregation induced via CD98 and CD29 could also be distinguished by the pat tern of protein tyrosine phosphorylation induced. Some CD29 antibodies part ially inhibited CD98-induced aggregation, and these antibodies were neither agonistic for aggregation nor inhibitors of beta1-integrin binding to subs trates. Conversely, some CD98 antibodies were potent inhibitors of CD29-ind uced aggregation. Antibodies to beta2 integrins also partially inhibited CD 29-induced aggregation. Unexpectedly, 2 antibodies to CD147, an immunoglobu lin superfamily member whose function has remained unclear, were also poten t inhibitors of both the aggregation and the protein tyrosine phosphorylati on induced via CD98 ligation. The results of this study support a central r ole for CD98 within a multimolecular unit that regulates cell aggregation. (C) 2001 by The American Society of Hematology.