Related Experiment Videos
Hepatic killing but not clearance of systemically circulating bacteria is dependent upon peripheral leukocytes via
Mathew L Brengman1, Dajie Wang, Kirsten B Wilkins
1Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Abstract:
The hepatic reticuloendothelial system (RES) is the primary mechanism for removing circulating bacteria from the systemic circulation. While Kupffer cells are important for this process, leukocytes appear to play a significant role as well. Hepatic leukocyte accumulation following ischemia/reperfusion or cytokine stimulation is well documented, but its contribution to phagocytic killing by the hepatic RES is not fully understood. We evaluated the role of leukocytes in general, and leukocyte-endothelial adhesion in particular, in hepatic RES function. This was done by inducing confirmed leukopenia with cyclophosphamide or by blocking leukocyte-endothelial adhesion molecules with specific blocking antibodies. Hepatic phagocytic clearance (HPC) and hepatic phagocytic killing (HKE) of systemically intravenously injected E. coli were assayed and quantitated by a validated dual isotope label technique. HPC among the various experimental groups and respective controls varied only slightly, with no statistically significant differences observed. Leukopenia or CD11b blockade each significantly decreased the HKE relative to the controls. Antibody blockade of certain other adhesion molecules had no significant effect on HKE (or HPC). The role of leukocytes in killing systemically circulating bacteria is an integral component of hepatic RES function. This capability of the leukocyte appears to be dependent, in part, on the adhesion molecule, Mac-1.
Insights
Leukocytes, not just Kupffer cells, are crucial for the liver's bacterial defense system. Blocking leukocyte adhesion molecules, particularly Mac-1, impairs the liver's ability to kill bacteria.
Area of Science:
- Immunology
- Hepatology
- Microbiology
Background:
- The liver's reticuloendothelial system (RES) primarily clears circulating bacteria.
- While Kupffer cells are key, the role of leukocytes in hepatic bacterial clearance is not fully understood.
- Hepatic leukocyte accumulation is known, but their phagocytic contribution requires further investigation.
Purpose of the Study:
- To evaluate the role of leukocytes in hepatic RES function.
- To determine the specific contribution of leukocyte-endothelial adhesion to bacterial killing.
- To investigate the impact of leukopenia and adhesion molecule blockade on hepatic bacterial clearance.
Main Methods:
- Inducing leukopenia using cyclophosphamide.
- Blocking leukocyte-endothelial adhesion molecules with specific antibodies.
- Quantifying hepatic phagocytic clearance (HPC) and killing (HKE) of E. coli using a dual isotope label technique.
Main Results:
- Hepatic phagocytic clearance (HPC) showed no significant differences across experimental groups.
- Leukopenia and CD11b blockade significantly reduced hepatic phagocytic killing (HKE).
- Blockade of other adhesion molecules did not significantly affect HKE or HPC.
Conclusions:
- Leukocytes play an integral role in the hepatic RES's ability to kill systemically circulating bacteria.
- Leukocyte-dependent bacterial killing is partially dependent on the Mac-1 adhesion molecule.
- Leukocyte function, specifically bacterial killing, is a critical component of liver immune defense.