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 th e most recently described members of the integrins participating in in tercellular binding. Their expression has been shown to be restricted to leukocytes and they have been suggested to be predominantly found i n lymphocytes associating with the epithelium. Expression of beta 7 ha s mainly been studied on lymphocytes whereas macrophages have been rep orted not to express the beta(7) integrins. In this paper we have stud ied the expression of IS7 integrins in monocytoid cells. The myelomono cytic cell lines HL-60 and THP-1 did not express beta(7) mRNA or prote in, but differentiation of these cell lines to macrophages with phorbo l 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 ce lls with interferon-gamma (IFN-gamma). However, its up-regulating effe ct 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, resp ectively) 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, sever al Act I+ and HML-1(+) macrophages were found in immunohistochemical s tainings of both liver and edemic lung biopsies as well as in lymph no de sinuses. We therefore conclude that while monocytes do not express beta(7) integrins the more differentiated cells of the monocyte-macrop hage lineage do express both the alpha(4) beta(7) and alpha(E) beta(7) integrins, which might play a role in their intraepithelial homing.