For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

Opsonization of apoptotic cells and its effect on macrophage and T cell immune responses.

TitleOpsonization of apoptotic cells and its effect on macrophage and T cell immune responses.
Publication TypeJournal Article
Year of Publication2003
AuthorsKim SJung, Gershov D, Ma X, Brot N, Elkon KB
JournalAnn N Y Acad Sci
Volume987
Pagination68-78
Date Published2003 Apr
ISSN0077-8923
KeywordsApoptosis, Autoantibodies, Complement System Proteins, Immunoglobulin M, Macrophages, Opsonin Proteins, T-Lymphocytes
Abstract

Genetic studies in mice indicate that predisposition to lupus-like diseases is caused by at least three mechanisms: (1) alterations in the threshold of activation of lymphocytes or macrophages; (2) defective signaling for activation-induced cell death; and (3) reduced clearance of apoptotic cells. To define the mechanisms whereby lupus develops in mice with deficiencies in either C1q, serum amyloid P component (SAP, the mouse counterpart of C-reactive protein, or CRP), or serum IgM, we studied the efficiency of phagocytosis of apoptotic cells using serum with varying levels of C1q, CRP, or IgM; we also examined the immune response to ingestion of dying cells under these conditions. Deficiency of C1q led to impaired macrophage phagocytosis of apoptotic cells, whereas CRP augmented phagocytosis, largely through recruitment of the early complement components. Like CRP, normal polyclonal IgM bound to apoptotic cells and activated complement on the cell surface. Similarly, direct binding as well as absorption experiments revealed that CRP and IgM antibodies had a similar ligand recognition specificity, namely lysophospholipids containing phosphorylcholine. IL-12 provides a pivotal link between macrophages and the T cell response to ingested material. We observed that necrotic cells induced IL-12 p40 expression, whereas phagocytosis of apoptotic cells profoundly reduced IL-12 production from stimulated macrophages. Furthermore, soluble factors from macrophages that had ingested apoptotic cells suppressed interferon-gamma production by activated T cells. These findings suggest that phospholipid exposure on apoptotic cells promotes opsonization by serum proteins leading to activation of complement, macrophage ingestion, and T cell suppression. We discuss how deficient opsonization or processing of dying cells leads to autoimmunity.

DOI10.1111/j.1749-6632.2003.tb06034.x
Alternate JournalAnn N Y Acad Sci
PubMed ID12727625

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587