The Influence of the Spleen on Neutrophil Apoptosis in Vivo

Abstract

Abstract:In contrast to radiolabelled erythrocytes and platelets, radiolabelled neutrophils leave the circulating blood in an exponential manner, indicating random rather than age-dependent removal. Neutrophils transit the spleen with a range of residence times that are log normally distributed. We hypothesized that neutrophils are conditioned to undergo apoptosis to an extent that depends on their intrasplenic residence time and that this provides an explanation for the random removal of these cells from blood. Splenic venous and peripheral arterial blood was sampled simultaneously during abdominal surgery in four patients and age-dependent apoptosis assessed in whole blood using annexin V/PI staining. Apoptosis increased after 4 and 20 h ex-vivo incubation and was invariably higher in splenic venous vs arterial neutrophils. Transit through the spleen appears to promote neutrophil apoptosis, with subsequent high efficiencyclearancebytheliver.Thismayexplainthemechanismunderlyingtherandomremovalofneutrophilsfromtheblood.

Splenectomy is Associated with Altered Leukocyte Kinetics after Severe Trauma

“…A mean (std) Glasgow Coma Scale-score of 14 (9-15) was encountered. The mean ISS (std) of our population was 29 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). The mean (std) systolic blood pressure on admission was 120 (110-137) mmHg, a mean (std) heart rate of 90 (76-110) beats per minute was documented and overall injury severity was further re ected by a mean (std) admission serum Hemoglobin level of 8.0 (7.2-8.9) g/dl.…”

“…High levels of membrane expression of CD16 are associated with phenotypical features of a more matured neutrophil population [28]. Moreover, a comparison between afferent and efferent splenic vessels suggests that the spleen promotes and modi es neutrophil apoptosis in vivo [30]. We therefore propose that the spleen modulates neutrophil clearance and the enhanced and long-lasting leukocytosis seen after splenectomy vs. nonoperatively managed trauma patients might be due to inadequate acute neutrophil clearance.…”

“…We identi ed a persistent state of leukocytosis in splenectomized polytrauma patients which may be the result of decreased neutrophil apoptosis as a consequence of asplenia, and subsequent prolonged survival of competent immune cells incapable of extravasating into tissue compartments [27][28][29][30]. Alternatively, asplenia may 1) stimulate an increased bone marrow release of immune cells or 2) enhance immune cell re-migration from the tissue compartment back into circulation.…”

Splenectomy is associated with altered leukocyte kinetics after severe trauma

“…We identified a persistent state of leukocytosis in splenectomized polytrauma patients which may be the result of decreased neutrophil apoptosis as a consequence of asplenia, and subsequent prolonged survival of competent immune cells incapable of extravasating into tissue compartments [ 29 – 32 ]. Alternatively, asplenia may (1) stimulate an increased bone marrow release of immune cells or (2) enhance immune cell re-migration from the tissue compartment back into circulation.…”

“…High levels of membrane expression of CD16 are associated with phenotypical features of a more matured neutrophil population [ 30 ]. Moreover, a comparison between afferent and efferent splenic vessels suggests that the spleen promotes and modifies neutrophil apoptosis in vivo [ 32 ]. We, therefore, propose that the spleen modulates neutrophil clearance and the enhanced and long-lasting leukocytosis seen after splenectomy vs. nonoperatively managed trauma patients might be due to inadequate acute neutrophil clearance.…”