Do Lipocalins Play a Role in Mast Cell Physiology?.

Introduction. Aiming to identify molecular properties of allergens responsible for their “intrinsic allergenicity”, we focus on a subset of xenogeneic lipocalins (LCs) that comprise the major mammalian respiratory allergens. These structurally and functionally homologous molecules likely possess conserved molecular motifs promoting IgE-dependent allergy. We hypothesize that such LC “allergenicity” depends on non-IgE interactions of LCs with components of the innate immune system. Herein we describe a possible basis for such interactions between LCs and mast cells.

Materials and Methods. Two sources of human mast cells were used; primary cultures derived from peripheral blood CD34+ progenitor cells; or the LAD-2 cell line. Cells were cultured in serum-free medium with recombinant human stem cell factor (SCF; 100 ng/ml). Monoclonal antibodies to human gp330/megalin (MAb E11) were a kind gift of Prof. Lars Rask (Uppsala University, Sweden). Cell surface protein expression was assessed by flow cytometry and gene transcription was measured by real-time PCR.

Results. Monoclonal antibodies to an endocytic cell surface receptor (megalin, also known as low-density lipoprotein receptor-related protein (LRP)-2) known to bind multiple LCs stained the mast cell lines. This putative expression of megalin by the mast cells corresponded to their transcription of megalin mRNA as shown as by PCR. Moreover, mast cell megalin gene transcription could be induced (≥ 1000-fold) by overnight culture with monomeric IgE myeloma protein (100 ng/ml), and such induction of the megalin message correlated with both an increase in cell surface expression of the molecule and the specific binding of a purified human LC (a-1 microglobulin).

Conclusion. Megalin, an LC-binding cell surface receptor, appears to be constitutively expressed by both progenitor and mature mast cells, and its expression seems to be strongly upregulated by culture with monomeric IgE. This is consistent with a role for direct mast cell-LC interactions in the development of IgE-dependent allergy. In addition, and also of potential clinical relevance, endogenous LCs may play a functional role in normal mast cell physiology.