Background: Mast cells exert profound pleiotropic effects on immune cell reactions at inflammatory sites, where they are most likely influenced not only by the extracellular matrix (ECM) and inflammatory mediators but also by the proximity of activated T lymphocytes. We recently reported that activated T cells induce mast cell degranulation with the release of TNF-alpha, and that this activation pathway is mediated by lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) binding.
Objective: To determine how this contact between the two cell types can modulate mast cell behaviour in an inflammatory milieu by examining the adhesion of mast cells to endothelial cells and ECM ligands in an integrin-dependent manner.
Methods: Human mast cells (HMC-1) were co-cultured with resting or activated T cells followed by testing their adhesion to endothelial cell and ECM ligands, stromal derived factor-1alpha (SDF-1alpha)-induced migration, and western blotting.
Results: Co-culturing HMC-1 with activated, but not with resting T cells resulted in marked stimulation of mast cell adhesion to vascular cell adhesion molecule-1 and ICAM-1 in a very late antigen-4- and LFA-1-dependent fashion. In addition, activated T cells or T cell membranes promoted HMC-1 adhesion to fibronectin (FN) and laminin. This effect was accompanied by the phosphorylation of extracellular regulated kinase and p38, but not of c-Jun N-terminal kinase. Importantly, the adhesive property of mast cells depended exclusively on the direct contact between the two cell types, since neither supernatants from activated T cells nor separation of the two cell populations with a porous membrane affected mast cell adhesion to FN. Furthermore, similar results were obtained when mast cells were incubated with purified membranes from activated T cells. These results suggest that, in addition to stimulating mast cell degranulation, the proximity of activated T lymphocytes to mast cells can mediate the adhesion of mast cell precursors to the endothelial ligands and ECM. Activated T cells also stimulated SDF-1alpha-induced mast cell migration.
Conclusion: This symbiotic relationship between the two types of immune cells may serve to direct mast cells to specific sites of inflammation where their effector functions are required.