Self-regulation of neutrophils during phagocytosis is modified after severe tissue injury

Abstract

Neutrophil (PMNL) function is influenced by factors released by other immune cells during the course of the immune response. We investigated the effect of neutrophil cell density and the effect of supernatant of the phagocytosis assay on the phagocytosis activity of PMNLs. The measurements were carried out with naive (control) PMNLs of healthy donors and with PMNLs obtained from patients with severe tissue injury. Phagocytosis index (FI) of PMNLs was determined at cell densities of 7.5x10 5 /ml and 15x10 5 /ml. E. coli phagocytosis of heparinized whole blood from healthy donors and patients with severe tissue injury was measured and evaluated at three different cell densities (normal, half, and double densities) by flow cytometry. Supernatants of phagocytosis assays of either control or trauma (ISS >18) patient PMNLs were added to the assay suspensions of control and trauma PMNLs. An increase in cell density of healthy donor PMNLs increased yeast phagocytic activity. In cases of tissue injury, PMNLs showed increased phagocytic activity at lower cell densities. E. coli phagocytosis was increased with the increase of cell density, and tissue injury PMNLs were more active at each cell concentration compared to naive cells. Polytrauma supernatants in most cases inhibited, while healthy supernatants mostly increased the yeast phagocytosis of healthy and trauma PMNLs. These results reinforce the idea that primed PMNLs in the presence of microbial agents produce factor(s) which inhibit some of the cell's antimicrobial functions contributing to immunedysfunction, while unprimed PMNLs produce factor(s) which facilitate antimicrobial countermeasure. These results also demonstrate that reduced phagocytosis of tissue injury primed PMNLs is not due to cytoskeletal changes but to the humoral environment.

Does Neutrophil Phenotype Predict the Survival of Trauma Patients?

“…Some reports have demonstrated decreased neutrophil phagocytosis following trauma and injury, for example, the lowest rates of neutrophil phagocytosis were observed at 48 and 72 h after TBI (127). In contrast, the neutrophil phagocytosis index (FI) was higher 1–3 days after severe tissue injury (138). Generally, after trauma, ingestion of E coli was enhanced, whereas phagocytosis of K pneumoniae was depressed.…”

Mathematical Modelling of Immune Response in Tissues

“…It is known that neutrophils invading the site of an infection produce auto-inhibitory factors [54,77]. Since neutrophils produce the vast majority of infection site chemokine early in infection, we let the concentration of chemokine stand in for all such factors.…”

“…Finally, we introduce a self-regulation term d NjCH CH·N, involving the generic chemokine CH (see Section 2.6). Neutrophils are known to release many self-regulating molecules [14,54,77]. Since chemokine CH is predominately produced by neutrophils early in infection [see Equation (9)], we use CH levels to auto-regulate these cells.…”

Severe head injury promotes early caspase-dependent apoptosis in peripheral blood monocytes from multiply injured patients

“…In this regard, the limitations of our study become obvious and several confounding variables must be acknowledged. The host's innate immune response to trauma is highly complex and requires consideration of all key immunocompetent cells, including dendritic and natural killer cells, T lymphocytes and neutrophils (5,41,42). Moreover, tissue-specific alterations otherwise not detected in human in vivo analyses may comparably predispose to local defective antigen presentation, loss of phagocytic potential and deregulated cytokine production with consecutive systemic effects (43).…”