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Macrophage scavenger receptor(s) and oxidatively modified proteins in endometriosis
A A Murphy1, W Palinski, S Rankin
1Department of Gynecology and Obstetrics, Emory University, Atlanta, Georgia 30322, USA.
Objective:
To determine whether cultured human peritoneal macrophages have functional scavenger receptor(s) and whether activation of macrophages in endometriosis may involve an increase in scavenger receptor activity.
Design:
A controlled clinical study comparing peritoneal fluid (PF) macrophages of women with endometriosis and controls without endometriosis.
Setting:
Women undergoing laparoscopic evaluation and treatment in a tertiary medical center.
Patient(S):
Twenty-one women undergoing evaluation for pelvic pain or infertility and 10 women undergoing elective laparoscopic tubal ligation.
Intervention(S):
None.
Main Outcome Measure(S):
Evidence for functional macrophage scavenger receptor and evidence of ligands for the scavenger receptor in PF.
Result(S):
Peritoneal macrophages of women with endometriosis degrade significantly more endothelial cell-low density lipoprotein (EC-LDL) and copper-oxidized LDL (Cu-LDL) than native LDL. Macrophages of women with endometriosis also incorporate more labeled oleic acid into cholesteryl ester in the presence of oxidized LDL (Ox-LDL) than in the presence of native LDL. Western blot analysis demonstrates the presence of adducts between lipid peroxidation products and proteins in PF of patients with and without endometriosis. The PF of women with endometriosis competes with labeled Ox-LDL for uptake by mouse peritoneal macrophages in a dose-dependent manner.
Conclusion(S):
We demonstrate for the first time that human macrophages have functional scavenger receptor(s) and that activation of macrophages in endometriosis involves an increase in scavenger receptor activity. Two lines of evidence indicate the presence of ligands for the scavenger receptor in PF.
Insights
Human peritoneal macrophages possess functional scavenger receptors. Macrophages in endometriosis exhibit increased scavenger receptor activity, suggesting a role in the condition's pathogenesis.
Area of Science:
- Immunology
- Reproductive Biology
- Cell Biology
Background:
- Macrophages play a crucial role in the immune response within the peritoneal cavity.
- Endometriosis is a chronic inflammatory condition characterized by the presence of endometrial tissue outside the uterus.
- Dysregulated macrophage activity is implicated in the pathophysiology of endometriosis.
Purpose of the Study:
- To investigate the presence and function of scavenger receptors on human peritoneal macrophages.
- To determine if scavenger receptor activity is altered in women with endometriosis.
Main Methods:
- A controlled clinical study comparing peritoneal fluid macrophages from women with and without endometriosis.
- Analysis of macrophage degradation of low-density lipoprotein (LDL) variants (EC-LDL, Cu-LDL, Ox-LDL).
- Western blot analysis to detect lipid peroxidation adducts and competitive uptake assays.
Main Results:
- Peritoneal macrophages from women with endometriosis showed significantly higher degradation of oxidized LDL (Ox-LDL) compared to native LDL.
- Macrophages from endometriosis patients incorporated more oleic acid into cholesteryl ester when exposed to Ox-LDL.
- Peritoneal fluid from women with endometriosis competed with labeled Ox-LDL for uptake by macrophages, indicating the presence of scavenger receptor ligands.
Conclusions:
- Human peritoneal macrophages possess functional scavenger receptors.
- Macrophage activation in endometriosis involves increased scavenger receptor activity.
- Ligands for scavenger receptors are present in the peritoneal fluid of women with endometriosis.