@Article{ecn.2014.0345,
AUTHOR = {Randeep S. Jawa, Erin Quist, Craig W. Boyer, Valerie K. Shostrom, David W. Mercer},
TITLE = {Mesenteric ischemia-reperfusion injury up-regulates certain CC, CXC, and XC chemokines and results in multi-organ injury in a time-dependent manner*},
JOURNAL = {European Cytokine Network},
VOLUME = {24},
YEAR = {2013},
NUMBER = {4},
PAGES = {148--156},
URL = {http://www.techscience.com/ECN/v24n4/65626},
ISSN = {1952-4005},
ABSTRACT = {Introduction: Trauma patients who develop multi-organ dysfunction have increased systemic
levels of chemotactic cytokines. Ischemia-reperfusion (IR) injury to the gut may play a role. The purpose of this
study was to examine chemokine production in a mouse model of mesenteric IR injury. Given the pre-eminent
role of the neutrophil, there has been much investigation of the CXC chemokines, but very limited research on
the CC and XC chemokines. We hypothesized that intestinal IR injury would induce remote organ injury and
enhance serum CC and XC chemokine levels. Methods: Fasted female C57BL6 mice were anesthetized prior to
laparotomy. In IR animals, the superior mesenteric artery (SMA) was occluded for 30, 45, or 75 min, while controls
underwent sham laparotomy, n = 5-7 per group. After the indicated time point, the incision was closed and
the mouse was allowed to recover for six hours. Following euthanasia, serum levels of 15 chemokines (10 CC, 4
CXC, and 1 XC) were assessed and histopathologic analyses performed. Results: Seventy-five minutes of SMA
occlusion was the key time frame for significant serum cytokine level up-regulation, intestinal and remote organ
injury, and neutrophil influx into tissues. With 75 min of intestinal ischemia, significantly elevated serum levels, as
compared to shams, were noted for seven CC chemokines: MCP-1, MCP-3, MIP-1β, MIP-3β, eotaxin, MDC, and
RANTES. Levels of the XC chemokine lymphotactin also increased. Levels of MIP-2, IP-10, and KC/GRO (CXC
chemokines) rose significantly. MIP-1α levels were only significantly increased at 45 min IR. We did not find any
significant IR injury-induced changes in levels of MCP-5, MIP-1γ, or GCP-2, at any ischemia time frame. Serum
levels of IL-6 correspondingly increased significantly with longer ischemia times. Conclusions: The novel finding
of this study is the demonstration of significant systemic increases in the CC chemokines eotaxin, MCP-3, MDC,
MIP-3β in a time-dependent manner, along with tissue injury. The data suggest a complex response to IR injury
whereby chemokines that are active on a variety of leukocytes may play a role in inducing local and remote tissue
injury.},
DOI = {10.1684/ecn.2014.0345}
}