Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation.
We have cloned a novel mouse CC chemokine cDNA from the lung during an allergic inflammatory reaction. The protein encoded by this cDNA is chemotactic for eosinophils, monocytes, and lymphocytes in vitro and in vivo. Based on its similarities in sequence and function with other CC chemokines, we have named it mouse monocyte chemotactic protein-5 (mMCP-5). Under noninflammatory conditions, expression of mMCP-5 in the lymph nodes and thymus is constitutive and is generally restricted to stromal cells. Neutralization of mMCP-5 protein with specific antibodies during an allergic inflammatory reaction in vivo resulted in a reduction in the number of eosinophils that accumulated in the lung. Moreover, mMCP-5 mRNA expression in vivo is regulated differently from that of other major CC chemokines in the lung during the allergic reaction, including Eotaxin. The presence of lymphocytes is essential for expression of mMCP-5 by alveolar macrophages and smooth muscle cells in the lung, and the induction of mMCP-5 RNA occurs earlier than that of the eosinophil chemokine Eotaxin during allergic inflammation. In contrast to Eotaxin, mRNA for mMCP-5 can be produced by mast cells. From these results, we postulate that mMCP-5 plays a pivotal role during the early stages of allergic lung inflammation.
Jia
G Q
GQ
Center for Blood Research, Inc., Harvard Medical School, Boston, Massachusetts 02115, USA.
Gonzalo
J A
JA
Lloyd
C
C
Kremer
L
L
Lu
L
L
Martinez-A
C
C
Wershil
B K
BK
Gutierrez-Ramos
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000235:genetics; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D016207:Cytokines / Q000494:pharmacology; D004347:Drug Interactions; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000145:classification / Q000235:genetics* / Q000494:pharmacology*; D010529:Peritoneal Cavity / Q000166:cytology; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D017252:CD3 Complex; C515457:Ccl11 protein, mouse; C491224:Ccl12 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D018398:Homeodomain Proteins; D018945:Monocyte Chemoattractant Proteins; D011506:Proteins; D012333:RNA, Messenger; C064658:RAG-1 protein