Alpha E beta 7 and alpha 4 beta 7 integrins associated with intraepithelial and mucosal homing, are expressed on macrophages.

The two beta 7 integrins alpha E beta 7 and alpha 4 beta 7 are the most recently described members of the integrins participating in intercellular binding. Their expression has been shown to be restricted to leukocytes and they have been suggested to be predominantly found in lymphocytes associating with the epithelium. Expression of beta 7 has mainly been studied on lymphocytes whereas macrophages have been reported not to express the beta 7 integrins. In this paper we have studied the expression of beta 7 integrins in monocytoid cells. The myelomonocytic cell lines HL-60 and THP-1 did not express beta 7 mRNA or protein, but differentiation of these cell lines to macrophages with phorbol 12-myristate 13-acetate (PMA) led to a strong induction of the beta 7 mRNA expression. A clear but less pronounced up-regulation of beta 7 mRNA-expression was also seen after treatment of HL-60 and THP-1 cells with interferon-gamma (IFN-gamma). However, its up-regulating effect on the surface expression of alpha 4 beta 7 and alpha E beta 7 complexes (detected by the monoclonal antibodies Act I and HML-1, respectively) exceeded that observed with PMA. To verify the in vitro cell line observations with normal cells, we also studied peripheral blood monocytes and tissue macrophages. Peripheral blood monocytes were Act I- and HML-1- in flow cytometry, but their expression was increased after a 72-h culture in the presence of PMA or IFN-gamma. Also, several Act I+ and HML-1+ macrophages were found in immunohistochemical stainings of both liver and edemic lung biopsies as well as in lymph node sinuses. We therefore conclude that while monocytes do not express beta 7 integrins the more differentiated cells of the monocyte-macrophage lineage do express both the alpha 4 beta 7 and alpha E beta 7 integrins, which might play a role in their intraepithelial homing.