Regulation of mast cell migration by TH1 and TH2 cytokines:: Identification of tumour necrosis factor-α and interleukin-4 as mast cell chemotaxins

Mast cells act as central effector and regulatory cells in many inflammatory disorders, including T helper 1 (T-H1)-mediated inflammations such as autoimmunity and T-H2-mediated inflammations such as allergy and parasite infections. One characteristic for mast cell-mediated inflammations is the accumulation of mast cells in the inflamed tissue. The factors regulating mast cell recruitment in these inflammations are still not fully characterized. We have investigated the potency of T-H1- and T-H2-secreted cytokines to mediate mast cell migration. Supernatants from six different T-H1 and T-H2 clones were tested for mast cell-chemotactic activity using the human mast cell line (HMC-1) as a responder cell. All six clones produced factors that induced mast cell migration. Using blocking antibodies to a broad range of cytokines, we found that anti-tumour necrosis factor-alpha (anti-TNF-alpha) reduced the migration of mast cells to supernatants from T-H1 clones. In contrast, the main mast cell chemoattractants secreted by T-H2 clones were found to be interleukin-4 (IL-4) and IL-8. The potency of these cytokines to act as mast cell chemoattractants was confirmed by using recombinant IL-4, IL-8 and TNF-alpha. Our results suggest that TNF-alpha can be involved in the recruitment of mast cells in T-H1-mediated inflammations, whereas IL-4 and IL-8 might play a similar role in T-H2-mediated inflammations.