The functional interactions between CD98, beta1-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 immunobiology. In this study, the functional interactions between CD98 and other adhesion molecules on the surface of the promonocyte line U937 are examined by means of a quantitative assay of cell aggregation. Several of the CD98 antibodies induced homotypic aggregation of these cells without affecting cellular viability or growth. Aggregation induced by CD98 antibodies could be distinguished from that induced by beta1-integrin (CD29) ligation by lack of sensitivity to EDTA and by increased sensitivity to deoxyglucose. Aggregation induced via CD98 and CD29 could also be distinguished by the pattern of protein tyrosine phosphorylation induced. Some CD29 antibodies partially inhibited CD98-induced aggregation, and these antibodies were neither agonistic for aggregation nor inhibitors of beta1-integrin binding to substrates. Conversely, some CD98 antibodies were potent inhibitors of CD29-induced aggregation. Antibodies to beta2 integrins also partially inhibited CD98-induced aggregation. Unexpectedly, 2 antibodies to CD147, an immunoglobulin superfamily member whose function has remained unclear, were also potent inhibitors of both the aggregation and the protein tyrosine phosphorylation induced via CD98 ligation. The results of this study support a central role for CD98 within a multimolecular unit that regulates cell aggregation.