Mouse monocyte-derived chemokine is involved in airway hyperreactivity and lung inflammation.
The cloning, expression, and function of the murine (m) homologue of human (h) monocyte-derived chemokine (MDC) is reported here. Like hMDC, mMDC is able to elicit the chemotactic migration in vitro of activated lymphocytes and monocytes. Among activated lymphocytes, Th2 cells were induced to migrate most efficiently. mMDC mRNA and protein expression is modulated during the course of an allergic reaction in the lung. Neutralization of mMDC with specific Abs in a model of lung inflammation resulted in prevention of airway hyperreactivity and significant reduction of eosinophils in the lung interstitium but not in the airway lumen. These data suggest that mMDC is essential in the transit/retention of leukocytes in the lung tissue rather than in their extravasation from the blood vessel or during their transepithelial migration into the airways. These results also highlight the relevance of factors, such as mMDC, that regulate the migration and accumulation of leukocytes within the tissue during the development of the key physiological endpoint of asthma, airway hyperreactivity.
Gonzalo
J A
JA
Millennium Pharmaceuticals, Inc., Cambridge, MA 02139, USA.
Pan
Y
Y
Lloyd
C M
CM
Jia
G Q
GQ
Yu
G
G
Dussault
B
B
Powers
C A
CA
Proudfoot
A E
AE
Coyle
A J
AJ
Gearing
D
D
Gutierrez-Ramos
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D003888:Desensitization, Immunologic; D006801:Humans; D007106:Immune Sera / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
C515482:CCL22 protein, human; C515354:CCR4 protein, human; C515483:Ccl22 protein, mouse; C515355:Ccr4 protein, mouse; D054422:Chemokine CCL22; D019742:Chemokines, CC; D007106:Immune Sera; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D002118:Calcium