Monocyte chemotactic protein-1 (MCP-1), -2, and -3 are chemotactic for human T lymphocytes.
Monocyte chemotactic protein (MCP)-1, -2, and -3 all have been shown to induce monocyte/macrophage migration in vitro and MCP-1, also known as MCAF, chemoattracts basophils and mast cells. We report here that natural MCP-1 as well as synthetic preparations of MCP-2 and MCP-3 stimulate significant in vitro chemotaxis of human peripheral blood T lymphocytes. This MCP-induced migration was dose-dependent and directional, but not chemokinetic. Phenotypic analysis of the T cell population responsive to MCP-1, MCP-2, and MCP-3 demonstrates that both CD4+ and CD8+ T cells migrated in response to these chemokines. Similar results were observed using human CD4+ and CD8+ T cell clones. Neutralizing antisera to MCAF or MCP-2 abrogated T cell migration in response to MCP-1 and MCP-2, respectively, but not to RANTES. Subcutaneous administration of purified MCP-1 into the hind flanks of SCID mice engrafted with human peripheral blood lymphocytes (PBL) induced significant human CD3+ T cell infiltration into the site of injection at 4 h. These results demonstrate that MCP-1, MCP-2, and MCP-3 are inflammatory mediators that specifically stimulate the directional migration of T cells as well as monocytes and may play an important role in immune cell recruitment into sites of antigenic challenge.
Taub
D D
DD
Clinical Services Program, Program Resources, Inc., DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702.
Proost
P
P
Murphy
W J
WJ
Anver
M
M
Longo
D L
DL
van Damme
J
J
Oppenheim
J J
JJ
D000818:Animals; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016207:Cytokines; D004305:Dose-Response Relationship, Drug; D006133:Growth Substances / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D018945:Monocyte Chemoattractant Proteins; D012867:Skin / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects*
C515450:CCL7 protein, human; C515453:CCL8 protein, human; C515451:Ccl7 protein, mouse; C515454:Ccl8 protein, mouse; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors; D016207:Cytokines; D006133:Growth Substances; D018945:Monocyte Chemoattractant Proteins