Chloroquine, an anti-malarial agent, acts as a novel regulator of beta 1-integrin-mediated cell-cell adhesion.

Chloroquine is one of the disease-modifying antirheumatic drugs (DMARDs) with anti-malarial effect. In this study, we examined the modulatory effect of chloroquine on the functional activation of beta1-integrins (CD29) using CD29- and CD98 (a functional regulator of CD29)-mediated U937 cell-cell adhesion, comparing macrophage functions and T cell proliferation. Chloroquine effectively suppressed U937 cell-cell adhesion mediated by CD29 and CD98, in a protein kinase (PK) C, PKA, protein tyrosine kinase (PTK), extracellular signal-regulated kinase (ERK) and actin cytoskeleton-independent manner. Other lysomotropic agents (monesin, methylamine and ammonium chloride) also significantly diminished both CD29- and CD98-mediated cell-cell adhesion, indicating that lysomotropic character may play a critical role in regulating beta1-integrin functions. Therefore, these results suggest that chloroquine may act as a novel regulator of CD29 function in a lysomotropic character-dependent novel manner.