Fas-mediated apoptosis of neutrophils in sera of patients with infection

In the presence of infection, neutropenia is considered to be a marker of p oor prognosis; conversely, neutrophilia may not be a determinant of a bette r prognosis, Since apoptotic neutrophils are compromised functionally, we e valuated the effect of infection on neutrophil apoptosis, The rate of apopt osis was greater for neutrophils isolated from patients with infection than for healthy controls. Escherichia coli did not directly modulate the rate of neutrophil apoptosis, However, sera from infected patients promoted (P < 0.001) neutrophil apoptosis, Interestingly, the sera of patients with diff erent types of infection (gram negative, gram positive, or culture negative ) exerted a more or less identical response on neutrophil apoptosis, Sera o f infected patients showed a fivefold greater content of Fast compared to c ontrols. Moreover, anti-Fast antibody partly attenuated the infected-serum- induced neutrophil apoptosis. In in vitro studies, E. call enhanced monocyt e Fast expression. Moreover, conditioned media prepared from activated macr ophages from control mice showed enhanced apoptosis of human as well as mou se neutrophils. On the contrary, conditioned media prepared from activated macrophages isolated from FasL-deficient mice induced only a mild degree of neutrophil apoptosis, These results suggest that neutrophils in patients w ith infection undergo apoptosis at an accelerated rate. Infection not only promoted monocyte expression of Fast but also increased Fast content of the serum. Because the functional status of apoptotic cells is compromised, a significant number of neutrophils mag not be participating in the body's de fense. Since neutrophils play the most important role in innate immunity, t heir compromised status in the presence of infection may transfer the host defense burden from an innate response to acquired immunity. The present st udy provides some insight into the lack of correlation between neutrophilia and the outcome of infection.