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C5a receptor and thymocyte apoptosis in sepsis
Author(s) -
Riedemann Niels C.,
Guo RenFeng,
Laudes Ines J.,
Keller Katie,
Sarma Vidya J.,
Padgaonkar Vaishalee,
Zetoune Firas S.,
Ward Peter A.
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0033fje
Subject(s) - apoptosis , annexin , thymocyte , sepsis , in vitro , c5a receptor , receptor , lipopolysaccharide , biology , immunology , microbiology and biotechnology , chemistry , cd8 , antigen , biochemistry , immune system , complement system
ABSTRACT In sepsis, apoptosis occurs in many different organs. The mediators responsible for induction of apoptosis are not clearly known, although there are some suggestions that C5a and the C5a receptor (C5aR) might be directly linked to apoptosis. In the cecal ligation/puncture (CLP) model of sepsis in rats, apoptosis occurs early in a variety of organs, especially in the thymus. We demonstrate that thymocytes from normal rats show specific, saturable, and high affinity binding of 125 I‐labeled recombinant rat C5a. C5a binding to thymocytes was significantly increased 3 h after CLP and also when thymocytes from normal rats were first incubated in vitro with lipopolysaccharide (LPS) or IL‐6. The expression of C5aR mRNA in thymocytes was markedly increased 3, 6, and 12 h after CLP and increased similarly when normal thymocytes were first exposed to LPS or IL‐6 in vitro . Thymocytes obtained 2 or 3 h after CLP and exposed in vitro to C5a, but not normal thymocytes, underwent increased apoptosis, as demonstrated by annexin‐V binding, coinciding with increased activation of caspases 3, 6, and 8. These data provide the first direct evidence that in the early onset of sepsis, increased expression of C5aR occurs in thymocytes, which increases their susceptibility to C5a‐induced apoptosis.