Eotaxin-induced eosinophil migration in the peritoneal cavity of ovalbumin-sensitized mice: mechanism of action.
Cell accumulation in response to i.p. administration of the C-C chemokine, eotaxin, was studied in vivo. OVA-sensitized mice, exhibiting blood eosinophilia, had greater eosinophil (Eø) accumulation in response to 500 ng of eotaxin at 6 h (vehicle-injected, 3.0 +/- 0.5 x 10(5); eotaxin-injected, 8.6 +/- 1.0 x 10(5)) than nonsensitized, eotaxin-injected mice (2.5 +/- 0.4 x 10(5)). A nonspecific neutrophil migration was observed in both vehicle- and eotaxin-injected cavities. The number of intact mast cells in the peritoneal lavages after eotaxin injection was significantly lower than that in vehicle-injected animals (0.8 +/- 0.3 x 10(4) vs 2.8 +/-0.6 x 10(4), respectively). When endogenous peritoneal mast cells were depleted with compound 48/80 before eotaxin administration, there was a 51% reduction in Eø accumulation. This suggests an important role for endogenous mast cells in mediating the actions of eotaxin. The potential role of mast cell mediators in the actions of eotaxin was also investigated. Pretreatment with histamine-H1 or serotonin antagonists reduced Eø migration in response to eotaxin by 50 to 65%. Further, following pretreatment with a specific mAb against TNF-alpha, only nonspecific neutrophil influx was attenuated. Using neutralizing mAbs, Eø migration was found to be dependent on the adhesion molecules P- and E-selectin and CD11b. Eø accumulation was also sensitive to dexamethasone, with doses as low as 0.2 mg/kg inducing 100% inhibition. This study provides useful insight into the mechanisms of action of eotaxin.
Das
A M
AM
Department of Biochemical Pharmacology, The William Harvey Research Institute, London, United Kingdom. amdas@mds.qmw.ac.uk
Flower
R J
RJ
Perretti
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007114:Immunization; D018836:Inflammation Mediators / Q000502:physiology; D007958:Leukocyte Count; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D010529:Peritoneal Cavity / Q000166:cytology*
D000893:Anti-Inflammatory Agents; C515457:Ccl11 protein, mouse; D015815:Cell Adhesion Molecules; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D018836:Inflammation Mediators; D003907:Dexamethasone; D010047:Ovalbumin