C3A AND C5A STIMULATE CHEMOTAXIS OF HUMAN MAST-CELLS

The factors that control migration of mast cells to sites of inflammat ion and tissue repair remain largely undefined. Whereas several recent studies have described chemotactic factors that induce migration of m urine mast cells, only stem cell factor (SCF) is known to induce migra tion of human mast cells. We report here that the anaphylatoxins C3a a nd C5a are chemotactic factors for the human mast cell line HMC-1, hum an cord blood-derived mast cells (CBMC) and cutaneous mast cells in vi tro. The presence of an extracellular matrix protein, laminin, was req uired for chemotaxis in response to complement peptides. Migration of mast cells towards C3a and C5a was dose-dependent, peaking at 1 mu g/m L (100 nmol/L), and was inhibited by specific antibodies. Pretreatment with pertussis toxin inhibited the anaphylatoxin-mediated migration o f HMC-1 cells, indicating that Gi proteins are involved in complement- activated signal transduction pathways in human mast cells. Both C3a a nd C5a also induced a rapid and transient mobilization of intracellula r free calcium ([Ca2+](i)) in HMC-1 cells. Besides SCF, other chemotac tic factors tested, such as interleukin-3, nerve growth factor, transf orming growth factor beta, RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta, failed to stimulate migration of human mast cells. In summary, these findings indicate that C3a and C5a serve as chemotaxins for human mast cells. Anaphylatoxin-mediated recruitment of mast cell s might play an important role in hypersensitivity and inflammatory pr ocesses. (C) 1997 by The American Society of Hematology.