Functional effects of eotaxin are selectively upregulated on IL-5 transgenic mouse eosinophils.
Synergistic interactions between cytokines, chemokines and adhesion molecules may facilitate the selective recruitment of eosinophils into sites of allergic inflammation. Ovalbumin-sensitized IL5TG mice responded to antigen challenge with robust airway eosinophilia 24 and 72 hr post-exposure. Adhesion molecule expression and functional responsiveness of immune cells derived from IL5TG mice to various inflammatory mediators were evaluated. IL5TG-derived eosinophils, but not neutrophils, expressed higher levels of CD49d and CD11b relative to WT. Functional responsiveness to eotaxin was increased in IL5TG eosinophils as demonstrated by a 10x increase in its potency in producing actin polymerization and 3x increase in CD11b upregulation relative to WT. These data are consistent with increased CCR3 expression on IL5TG eosinophils. Responsiveness of eosinophils to LTB4 or MIP-1alpha was similar between WT and IL-5TG mice. These data provide evidence of synergy between eosinophil-specific cytokines and chemokines that may promote accumulation of this cell type under conditions of allergic inflammation in vivo.
Kudlacz
Elizabeth
E
Pfizer Global Research and Development, Groton, CT 06340, USA. elizabeth_m_kudlacz@groton.pfizer.com
Whitney
Carrie
C
Andresenl
Catharine
C
Conklyn
Maryrose
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000494:pharmacology*; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D004357:Drug Synergism; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D039441:Integrin alpha4 / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; C515457:Ccl11 protein, mouse; C515351:Ccr3 protein, mouse; D015815:Cell Adhesion Molecules; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D015848:Interleukin-5; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D039441:Integrin alpha4