Monocyte chemotactic protein-2, monocyte chemotactic protein-3, and fibroblast-induced cytokine. Three new chemokines induce chemotaxis and activation of basophils.
Cytokine-dependent mediator release from basophils and mast cells may play an important role in the pathogenesis of allergic and inflammatory conditions. Many C-C chemokines have been found to activate basophils and mast cells. We investigated the effect of three newly identified C-C chemokines, monocyte chemotactic protein-2 and -3 (MCP-2, MCP-3) and fibroblast-induced cytokine (FIC) on basophils and mast cells. We found that all three cytokines induced histamine secretion from basophils in a dose-dependent manner. The secretion of histamine was a Ca(2+)-dependent process. MCP-3 was the most potent activator of basophils. MCP-3 and FIC activated basophils from all study subjects, whereas the histamine release by MCP-2 was donor-dependent. The histamine-releasing activity of MCP-2, MCP-3, and FIC was compared with that of MCP-1, RANTES, and macrophage inflammatory protein-1 alpha using basophils from 10 donors. MCP-1 was the most potent among all the C-C chemokines. However, MCP-3 was nearly as potent. MCP-2, MCP-3, and FIC induced significant chemotaxis of basophils. None of the cytokines activated mouse peritoneal mast cells. The synthesis of mRNA for MCP-3 was investigated by reverse-transcription PCR using allergen-stimulated PBMC and bronchoalveolar lavage cells. Both MNC and bronchoalveolar lavage cells expressed mRNA for MCP-3. The results of this study indicate that MCP-2, MCP-3, and FIC are novel histamine-releasing factors.
Alam
R
R
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555.
Forsythe
P
P
Stafford
S
S
Heinrich
J
J
Bravo
R
R
Proost
P
P
Van Damme
J
J
D000485:Allergens / Q000502:physiology; D001483:Base Sequence; D001491:Basophils / Q000502:physiology*; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000502:physiology*; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006636:Histamine Release; D006801:Humans; D006967:Hypersensitivity / Q000503:physiopathology*; D017874:Immediate-Early Proteins / Q000502:physiology*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger / Q000235:genetics
D000485:Allergens; C515450:CCL7 protein, human; C515453:CCL8 protein, human; C515451:Ccl7 protein, mouse; C515454:Ccl8 protein, mouse; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors; D016207:Cytokines; D017931:DNA Primers; D017874:Immediate-Early Proteins; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger