In vitro assessment of chemokine receptor-ligand interactions mediating mouse eosinophil migration.
Eosinophil migration from circulation is controlled, in part, by chemokines through a family of G-protein-coupled chemokine receptors (CCR). Studies of human eosinophils have demonstrated that signaling through CCR3 receptors is a prominent pathway leading to chemotaxis, although several other receptor-ligand interactions also appear to mediate eosinophil recruitment. The availability of genetically unique strains of mice permits a reductionist approach to assess the signaling pathways in experimental models of human disease. However, despite similarities in these pathways between mice and humans, significant species differences exist, complicating the translation of results from animal models to humans. Purified mouse eosinophils were used in this study to investigate the chemokine receptor expression and the activities of 18 chemokines. Mouse eosinophils isolated from IL-5 transgenic mice expressed transcripts encoding the chemokine receptors CCR1, CCR2, CCR3, CCR5, CCR8, CXCR2, and CXCR4, but not CCR4. Mouse eosinophils also migrated in response to human and mouse eotaxin-1 and -2, but not human eotaxin-3. In addition, the induced migration of mouse eosinophils by TARC, MIP-1beta, and KC suggests that unidentified receptor-ligand interactions contribute to eosinophil recruitment. It is interesting that the potent chemoattractant of human eosinophils, RANTES, was unable to mediate mouse eosinophil migration. Furthermore, despite the ability of MIP-1alpha to bind receptors on purified mouse eosinophils, it was only able to induce significant eosinophil migration in a mixed splenocyte population and was unable to induce migration of highly purified eosinophils. Collectively, these observations reveal physiologically relevant distinctions in mechanisms mediating human and mouse eosinophil migration that potentially reflect evolutionary disparities between these species.
Borchers
Michael T
MT
Mayo Clinic Scottsdale, Scottsdale, Arizona 85259, USA.
Ansay
Tracy
T
DeSalle
Rob
R
Daugherty
Bruce L
BL
Shen
Huahao
H
Metzger
Michael
M
Lee
Nancy A
NA
Lee
James J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000097:blood; D018946:Chemokine CCL5 / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004804:Eosinophils / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000166:cytology
C515350:CCR3 protein, human; C515351:Ccr3 protein, mouse; D018946:Chemokine CCL5; D008024:Ligands; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D002118:Calcium