Glucocorticoid Augmentation of Macrophage Capacity for Phagocytosis of Apoptotic Cells Is Associated with Reduced p130Cas Expression, Loss of Paxillin/pyk2 Phosphorylation, and High Levels of Active Rac

• Published in: The Journal of immunology (1950) Vol. 167; no. 2; pp. 976 - 986
• Main Authors: Giles, Katherine M, Ross, Katherine, Rossi, Adriano G, Hotchin, Neil A, Haslett, Christopher, Dransfield, Ian
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.07.2001
• Subjects: Adjuvants, Immunologic - pharmacology; Apoptosis - drug effects; Apoptosis - immunology; Cas protein; Cells, Cultured; Crk-Associated Substrate Protein; Cytoskeletal Proteins - antagonists & inhibitors; Cytoskeletal Proteins - metabolism; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Dexamethasone - pharmacology; Focal Adhesion Kinase 2; Humans; Immunophenotyping; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Neutrophils - cytology; Neutrophils - immunology; p130 protein; Paxillin; Phagocytosis - drug effects; Phosphoproteins - antagonists & inhibitors; Phosphoproteins - biosynthesis; Phosphoproteins - metabolism; Protein-Serine-Threonine Kinases - biosynthesis; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt; pyk2 protein; Rac protein; Receptors, Immunologic - physiology; Retinoblastoma-Like Protein p130
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.2.976

Phagocytic clearance of apoptotic granulocytes has a pivotal role in determining an inflammatory outcome, resolution or progression to a chronic state associated with development of fibrotic repair mechanisms, and/or autoimmune responses. In this study, we describe reprogramming of monocyte to macrophage differentiation by glucocorticoids, resulting in a marked augmentation of their capacity for phagocytosis of apoptotic neutrophils. This monocyte/macrophage phenotype was characterized by decreased phosphorylation, and therefore recruitment of paxillin and pyk2 to focal contacts and a down-regulation of p130Cas, a key adaptor molecule in integrin adhesion signaling. Glucocorticoid-treated cells also displayed higher levels of active Rac and cytoskeletal activity, which were mirrored by increases in phagocytic capability for apoptotic neutrophils. We propose that changes in the capacity for reorganization of cytoskeletal elements induced by glucocorticoids are essential for efficient phagocytic uptake of apoptotic cells.