αEβ7 and α4β7 integrins associated with intraepithelial and mucosal homing, are expressed on macrophages

Abstract

The two β₇ integrins α_Eβ₇ and α₄β₇ 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 β₇ has mainly been studied on lymphocytes whereas macrophages have been reported not to express the β₇ integrins. In this paper we have studied the expression of β₇ integrins in monocytoid cells. The myelomonocytic cell lines HL-60 and THP-1 did not express β₇ 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 β₇ mRNA expression. A clear but less pronounced up-regulation of β₇ mRNA-expression was also seen after treatment of HL-60 and THP-1 cells with interferon-γ (IFN-γ). However, its up-regulating effect on the surface expression of α₄β₇ and α_E7 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-γ. 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 β₇ integrins the more differentiated cells of the monocyte-macrophage lineage do express both the α₄β₇ and α_Eβ₇ integrins, which might play a role in their intraepithelial homing.