Murine monocyte chemoattractant protein (MCP)-5: a novel CC chemokine that is a structural and functional homologue of human MCP-1.
The chemokines are a large family of cytokines that control the recruitment of leukocytes in immune and inflammatory responses. We describe the isolation of a novel murine CC chemokine that, based on its biological and structural features, we have named monocyte chemoattractant protein (MCP)-5. MCP-5 mapped to the CC chemokine cluster on mouse chromosome 11 and was most closely related to human MCP-1 in structure (66% amino acid identity). Purified recombinant MCP-5 protein was a potent chemoattractant for peripheral blood monocytes, was only weakly active on eosinophils at high doses, and was inactive on neutrophils. MCP-5 induced a calcium flux in peripheral blood mononuclear cells, but not in purified murine eosinophils or neutrophils. Consistent with these results, MCP-5 induced a calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and murine CCR2, a CC chemokine receptor expressed on monocytes. MCP-5 did not induce a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5. Constitutive expression of MCP-5 mRNA was detected predominantly in lymph nodes, and its expression was markedly induced in macrophages activated in vitro and in vivo. Moreover, MCP-5 expression was up-regulated in the lungs of mice following aerosolized antigen challenge of sensitized mice, and during the host response to infection with Nippostrongylus brasiliensis. These data indicate that MCP-5 is a novel and potent monocyte active chemokine that is involved in allergic inflammation and the host response to pathogens.
Sarafi
M N
MN
Infectious Disease Unit, Massachusetts General Hospital, Boston, USA.
Garcia-Zepeda
E A
EA
MacLean
J A
JA
Charo
I F
IF
Luster
A D
AD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000737:chemistry*; D002874:Chromosome Mapping; D017931:DNA Primers; D018076:DNA, Complementary; D006801:Humans; D007668:Kidney; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000737:chemistry* / Q000235:genetics* / Q000494:pharmacology; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection
C491224:Ccl12 protein, mouse; D018932:Chemokine CCL2; D017931:DNA Primers; D018076:DNA, Complementary; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; D002118:Calcium