title: Convergent alteration of granulopoiesis, chemotactic activity, and neutrophil apoptosis during mouse selection for high acute inflammatory response.
abstract: Neutrophil homeostasis was investigated in two mouse lines, AIRmax and AIRmin, genetically selected for high or low acute inflammatory response (AIR) and compared with unselected BALB/c mice. Mature neutrophil phenotype and functions appeared similar in the three mouse lines. However, an unprecedented phenotype was revealed in AIRmax animals characterized by a high neutrophil production in bone marrow (BM), a high number of neutrophils in blood, a high concentration of chemotactic agents in acrylamide-induced inflammatory exudates, and an increased resistance of locally infiltrated neutrophils to spontaneous apoptosis. In vitro, BM production of neutrophils and eosinophils was accompanied by an unusual high up-regulation of cytokine receptors as assessed by antibodies to CD131, which bind the common beta chain of receptors to interleukin (IL)-3, IL-5, and granulocyte macrophage-colony stimulating factor. An accelerated neutrophil maturation was also observed in response to all-trans retinoic acid. Several candidate genes can be proposed to explain this phenotype. Yet, more importantly, the results underline that genetic selection, based on the degree of AIR and starting from a founding population resulting from the intercross of eight inbred mouse lines, which display a continuous range of inflammatory responses, can lead to the convergent selection of alleles affecting neutrophil homeostasis. Similar gene combinations may occur in the human with important consequences in the susceptibility to inflammatory or infectious diseases and cancer.
authors.affiliation: Laboratoire d'Immunodifférenciation, EA 1556, Université Denis Diderot, Paris, France.
authors.forename: Orlando G
authors.initials: OG
authors.lastname: Ribeiro
authors.forename: Durvanei A
authors.initials: DA
authors.lastname: Maria
authors.forename: Sahil
authors.initials: S
authors.lastname: Adriouch
authors.forename: Séverine
authors.initials: S
authors.lastname: Pechberty
authors.forename: Wafa H K
authors.initials: WH
authors.lastname: Cabrera
authors.forename: Jean
authors.initials: J
authors.lastname: Morisset
authors.forename: Olga M
authors.initials: OM
authors.lastname: Ibañez
authors.forename: Michel
authors.initials: M
authors.lastname: Seman
mesh_terms: D000208:Acute Disease; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation; D002634:Chemotaxis, Leukocyte; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006410:Hematopoiesis; D007249:Inflammation / Q000097:blood*; D007958:Leukocyte Count; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor