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

Journal of Leukocyte Biology

Durvanei A. Maria²  Michel Seman¹  Olga M. Ibañez²  Sahil Adriouch¹  Wafa H. K. Cabrera²  Séverine Pechberty¹  Orlando G. Ribeiro³  Jean Morisset¹ 

[1] Laboratoire d’Immunodifférenciation, EA 1556, Université Denis Diderot, Paris, France; and Laboratoire d’Immunodifférenciation, EA 1556, Université Denis Diderot, Paris, France; and Laboratoire d’Immunodifférenciation, EA 1556, Université Denis Diderot, Paris, France; and;Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil;Laboratoire d’Immunodifférenciation, EA 1556, Université Denis Diderot, Paris, France; and Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil Laboratoire d’Immunodifférenciation, EA 1556, Université Denis Diderot, Paris, France; and Laboratoire d’Immunodifférenciation, EA 1556, Université Denis Diderot, Paris, France; and Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil Laboratoire d’Immunodifférenciation, EA 1556, Université Denis Diderot, Paris, France; and Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil

关键词: bone marrow;    polymorphonuclear neutrophils;    genetics;    polyacrylamide;    apoptosis;   

DOI  :  10.1189/jlb.0103039

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown