The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors

• Published in: Mediators of Inflammation Vol. 2015; no. 2015; pp. 498 - 509-245
• Main Authors: Xavier-Elsas, Pedro, da Silva, Cássio Luiz Coutinho Almeida, Vieira, Bruno Marques, Masid-de-Brito, Daniela, Queto, Túlio, de Luca, Bianca, Vieira, Thiago Soares de Souza, Gaspar-Elsas, Maria Ignez C.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01-01-2015; Hindawi Publishing Corporation; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Allergies; Amino acids; Animals; Bone marrow; Cytokines; Defects; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - pharmacology; Dosage and administration; Drug interactions; Eosinophils - cytology; Eosinophils - immunology; Experiments; Female; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Granulocytes - cytology; Granulocytes - drug effects; Granulocytes - immunology; Health aspects; Hematology; Lymphocytes; Lymphocytes - cytology; Lymphocytes - immunology; Male; Mice; Mice, Inbred C57BL; Neutrophils - cytology; Neutrophils - immunology; Observations; Pore Forming Cytotoxic Proteins - deficiency; Pore Forming Cytotoxic Proteins - genetics; Scholarships & fellowships; Transplants & implants
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2015/495430

Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp-) deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.