CD40 ligand expression correlates with resolution of peritonitis and mononuclear cell recruitment.
BACKGROUND
CD40 belongs to the tumor necrosis factor receptor family and its ligation is a central event in major inflammatory and immune reactions. We have previously demonstrated that CD40 ligation upregulates the secretion of mononuclear chemokines from peritoneal mesothelial cells (PMC), and that blocking the CD40 ligand (CD154) reduced the mononuclear infiltrate in a model of peritonitis.


OBJECTIVE
To characterize the kinetics of CD154 expression on peritoneal Leukocytes and examine the correlation of this occurrence with the mononuclear transition at the resolution phase of peritonitis.


METHODS
Leukocytes were collected from the effluent of 11 patients during episodes of peritonitis while undergoing peritoneal dialysis (PD). The effluent was then analyzed by flow cytometry to characterize CD154 expression.


RESULTS
CD154 expression on peritoneal mononuclear cells gradually increased during the resolution phase of peritonitis, peaking first on T cells (CD4+ and CD8* cells at 20-45 hours) and then on macrophages (CD14' at 20-50 hours). The maximal expression of CD154 on macrophages, CD4* cells, and CD8* cells during peak hours reached values of 33% * 23%, 4%-3%, and 24%-17%, respectively. The increase in CD154 expression was in-negative correlation (r= -0.44, p = 0.032) with total Leukocyte numbers and in positive correlation (r = 0.52, p = 0.009) with the increase of mononuclear cells. Deterioration of peritonitis was associated with a decrease in CD154 levels, while recurrence of peritonitis was related to high CD154 Levels.


CONCLUSIONS
Our data, which show a positive correlation between CD154 Levels and mononuclear dominance, suggest that CD40-CD154 Ligation plays an important role in the transition to mononuclear predominance in the late phase of peritonitis.
Department of Nephrology, Soroka Medical Center, Ben-Gurion University of the Negev, Faculty of Health Sciences, Beer Sheva, Israel.
Amir
A
Glik
Julia
J
Mazar
Boris
B
Rogachev
Moshe
M
Zlotnik
Amos
A
Douvdevani
D000328:Adult; D000368:Aged; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010529:Peritoneal Cavity / Q000473:pathology; D010538:Peritonitis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology / Q000378:metabolism
D019013:CD40 Antigens; D023201:CD40 Ligand