Convergent alteration of granulopoiesis, chemotactic activity, and neutrophil apoptosis during mouse selection for high acute inflammatory response

• Published in: Journal of leukocyte biology Vol. 74; no. 4; pp. 497 - 506
• Main Authors: Ribeiro, Orlando G., Maria, Durvanei A., Adriouch, Sahil, Pechberty, Séverine, Cabrera, Wafa H. K., Morisset, Jean, Ibañez, Olga M., Seman, Michel
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.10.2003
• Subjects: Acute Disease; Apoptosis; bone marrow; Bone Marrow Cells - physiology; Cell Differentiation; Chemotaxis, Leukocyte; genetics; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Inflammation - blood; Leukocyte Count; Neutrophils - immunology; Neutrophils - physiology; Platelet Endothelial Cell Adhesion Molecule-1 - analysis; polyacrylamide; polymorphonuclear neutrophils; Tretinoin - pharmacology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0103039

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 β 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.