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Changes in the response of neutrophils to endotoxin priming following major abdominal surgery
Yoshihiro Moriwaki1, Mitsugi Sugiyama, Yukihiro Ozawa
1Department of Critical Care and Emergency Medicine, Yokohama City University, School of Medicine, 4-57 Urafune-cho, Minami-ku, Yokohama, Japan. qqc3@urahp.yokohama-cu.ac.jp
Abstract:
Endotoxin (ETX) primes polymorphonuclear cells (PMNs) for the subsequent release of reactive oxygen species (ROS) in response to various stimulants such as phorbol myristate acetate (PMA). Although PMNs contribute to oxidative stress after stimulation by standard stimulants and after priming by many humoral factors, it is unknown whether the PMNs from patients at different postoperative times exhibit the same response to the same standard stimulant. We examined the response of PMA-induced production of ROS from PMNs at various intervals after major abdominal surgery in response to ETX priming. This study was a prospective clinical and laboratory study conducted over a 7-day period that involved 25 patients who were referred for elective major abdominal surgery (8 for gastric cancer, 9 for colonic cancer, 8 for rectal cancer). Blood was sampled on the day before operation and on postoperative days (PODs) 1, 3, and 7. For each sample we measured luminol-dependent chemiluminescence (CL), the time to peak counts (Tmax) of PMNs stimulated by PMA, and the serum ETX level. We studied the correlation between CL and ETX in samples from PODs 1 and 3. We also studied the CL of PMNs on PODs 1 and 3 preincubated (primed) with various concentrations of ETX (0, 20, 40, 60, and 100 pg/ml). We found that CL decreased on POD 1 compared with the preoperative level (p <0.05) because of the decreased Tmax. The level of CL per 1 ml of whole blood, however, was higher on PODs 1 and 3 than preoperatively. During this time, leukocytosis should compensate for the impaired production of ROS by an individual PMN. The serum ETX level was increased on POD 1 (p <0.05). There was a negative correlation between CL and ETX on POD 1 (correlation coefficient ?0.62, p < 0.01) and a positive correlation on POD 3 (0.61, p <0.01). CL on POD 3 was accelerated by ETX priming, but the CL on POD 1 was depressed by the priming using a low concentration of ETX. The mode of the response of PMNs to ETX priming differed between PODs 1 and 3. On POD 1 the responses of PMNs to environmental stimulants is suppressed, but by POD 3 these responses had increased.
Insights
Postoperative major abdominal surgery impairs polymorphonuclear cell (PMN) reactive oxygen species (ROS) production, with endotoxin (ETX) priming effects differing significantly between postoperative days 1 and 3.
Area of Science:
- Immunology
- Surgical Pathology
Background:
- Endotoxin (ETX) primes polymorphonuclear cells (PMNs) for reactive oxygen species (ROS) release.
- The impact of postoperative intervals on PMN responsiveness to ETX priming is not well understood.
Purpose of the Study:
- To investigate the effect of major abdominal surgery on PMN ROS production and ETX priming response over a 7-day postoperative period.
Main Methods:
- Prospective study of 25 patients undergoing major abdominal surgery.
- Blood samples collected preoperatively and on postoperative days (PODs) 1, 3, and 7.
- Measured luminol-dependent chemiluminescence (CL), time to peak counts (Tmax), and serum ETX levels; assessed ETX priming effects on PMN CL.
Main Results:
- PMN CL decreased on POD 1 due to reduced Tmax, despite increased overall CL per mL of blood (likely due to leukocytosis).
- Serum ETX levels increased on POD 1, correlating negatively with CL.
- ETX priming suppressed CL on POD 1 but enhanced it on POD 3, indicating altered PMN responsiveness.
Conclusions:
- Major abdominal surgery alters PMN function, suppressing responses on POD 1 and enhancing them by POD 3.
- The differential response to ETX priming highlights dynamic changes in PMN immunometabolism post-surgery.