CD40 ligand (CD154) takes part in regulation of the transition to mononuclear cell dominance during peritonitis.
BACKGROUND
CD40 is a member of the tumor necrosis factor (TNF) family of receptors whose ligand (CD154) is found mainly on membranes of activated mononuclear cells. CD154-CD40 cross-linking is a central event in antigen presentation, B-cell activation, and regulation of cytokine and chemokine secretion from various types of cells. We have previously demonstrated in vitro the presence of CD40 on human peritoneal mesothelial cells (PMC) and have also shown that CD40 ligation synergizes with interferon-gamma (IFN-gamma) to up-regulate CC chemokine secretion from these cells. The aim of the present study was to investigate the role of CD40 ligation in leukocyte recruitment during peritonitis.


METHODS
Peritonitis was induced in mice by bacterial inoculation, CD40 levels were analyzed on PMC by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. CD154 levels on leukocytes were analyzed by flow cytometry and RT-PCR. Chemokines mRNA levels were analyzed by RT-PCR. CD154 was blocked in vivo using monoclonal antibodies. Results. In mice inoculated by Staphylococcus epidermidis or Escherichia coli, CD40 in PMC increased twofold at 24 hours and CD154 was induced and reached a peak at 48 hours. In both Gram-positive and Gram-negative-peritonitis, peritoneal macrophages were the main peritoneal leukocyte population to express CD154. Similar results were observed in human subjects during peritonitis. Injection of CD154 blocking monoclonal antibody (MR1) reduced the mononuclear infiltrate by 50% and had no effect on granulocyte recruitment 48 hours after inoculation of S. epidermidis.


CONCLUSIONS
Our data suggest that CD40 plays a significant role in the process of the mononuclear infiltration during peritonitis.
Mazar
Julia
J
Department of Nephrology, Soroka University Medical Center, Ben-Gurion University of the Negev, Faculty of Health Sciences, Beer Sheva, Israel.
Agur
Timna
T
Rogachev
Boris
B
Ziv
Nadav Yehuda
NY
Zlotnik
Moshe
M
Chaimovitz
Cidio
C
Douvdevani
Amos
A
D000818:Animals; D001483:Base Sequence; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers; D004195:Disease Models, Animal; D004848:Epithelium / Q000276:immunology; D004927:Escherichia coli Infections; D005260:Female; D007150:Immunohistochemistry; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010538:Peritonitis / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013203:Staphylococcal Infections
D019013:CD40 Antigens; D017931:DNA Primers; D012333:RNA, Messenger; D023201:CD40 Ligand