MIGRATION RESPONSES OF HUMAN MONOCYTIC CELL-LINES TO ALPHA-CHEMOKINE AND BETA-CHEMOKINE

The beta-chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta and regulated on activation, normal T cells, expressed and secreted (RANTES) induced the in vitro migration of the monocytic cell line MonoMac-6. MCP-1 ex hibits the most potent chemotactic effect on this cell line while MIP- 1 alpha, RANTES and to a lesser extent MIP-1 beta were more moderate i nducers of cell migration, MonoMac-6 migration in response to chemokin es was shown to be a chemotactic and not a chemokinetic response, whic h was inhibited by pertussis and cholera toxins suggesting a role for G proteins in chemokine receptor-mediated signalling in these cells; c hemotaxis of MonoMac-6 cells in response to MCP-1 was abrogated by the addition of anti-MCP-1 antibody, The response of MonoMac-6 cells to t he alpha-chemokines IL-8, IP-10, growth-related peptide (Gro) alpha an d MIP-2 beta was substantially weaker than to the beta-chemokines, MCP -1 caused an alteration in cellular morphology by increasing ruffling at the cell membrane and the number of cells exhibiting extended pseud opodia, The chemotactic response of MonoMac-6 cells to beta-chemokines was compared with less well-differentiated myelomonocytic cell lines, THP-I showed a similar, but weaker response to the beta-chemokines wh ile both HL60 and U937 failed to respond to any member of this subfami ly when tested under the same conditions, These results suggest that t he differentiation status of cells of monocytic lineage may affect the ir response to beta-chemokines. (C) 1997 Academic Press Limited.