Production of the novel C-C chemokine MCP-4 by airway cells and comparison of its biological activity to other C-C chemokines.
Monocyte chemotactic protein-4 (MCP-4) is a newly identified C-C chemokine with potent eosinophil chemoattractant properties. We describe studies of its biological activity in vitro to induce chemotaxis of peripheral blood eosinophils and to induce histamine release from IL-3-primed peripheral blood basophils. MCP-4 and eotaxin caused a similar rise in eosinophil intracytoplasmic Ca2+ and complete cross-desensitization. MCP-4 also abolished the eosinophil Ca2+ response to MCP-3 and partially desensitized the response to macrophage inflammatory protein-1alpha. MCP-4 activated cell migration via either CCR2b or CCR3 in mouse lymphoma cells transfected with these chemokine receptors. MCP-4 inhibited binding of 125I-eotaxin to eosinophils and CCR3-transfected cells and inhibited 125I-MCP-1 binding to CCR2b-transfectants. MCP-4 mRNA was found in cells collected in bronchoalveolar lavage of asthmatic and nonasthmatic subjects and was prominently expressed in human lung and heart. MCP-4 mRNA was expressed in several human bronchial epithelial cell lines after cytokine stimulation. Pretreatment of BEAS-2B epithelial cells with the glucocorticoid budesonide inhibited MCP-4 mRNA expression. These features make MCP-4 a candidate for playing a role in eosinophil recruitment during allergic respiratory diseases.
Stellato
C
C
Johns Hopkins Asthma and Allergy Center, Division of Clinical Immunology, Baltimore, Maryland 21224, USA.
Collins
P
P
Ponath
P D
PD
Soler
D
D
Newman
W
W
La Rosa
G
G
Li
H
H
White
J
J
Schwiebert
L M
LM
Bickel
C
C
Liu
M
M
Bochner
B S
BS
Williams
T
T
Schleimer
R P
RP
D000595:Amino Acid Sequence; D000818:Animals; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019819:Budesonide; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured / Q000378:metabolism; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D054410:Chemokine CCL7; D019742:Chemokines, CC; D002633:Chemotaxis; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D018076:DNA, Complementary / Q000032:analysis; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D004847:Epithelial Cells; D006636:Histamine Release; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011282:Pregnenediones / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism
C515456:CCL11 protein, human; C099677:CCL13 protein, human; C515450:CCL7 protein, human; C515457:Ccl11 protein, mouse; C515451:Ccl7 protein, mouse; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D019742:Chemokines, CC; D016207:Cytokines; D018076:DNA, Complementary; D007377:Interleukin-3; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D011282:Pregnenediones; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D019819:Budesonide; D002118:Calcium