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Transient leukocytosis, granulocyte colony-stimulating factor plasma concentrations, and apoptosis determined by binding of annexin V by peripheral leukocytes in patients with severe sepsis.

This study was undertaken to clarify the relation between transient increases in the numbers of leukocytes and granulocyte colony-stimulating factor (G-CSF) plasma concentrations as well as the degree of apoptosis, as determined by binding of annexin V by these cells in patients with severe sepsis and septic shock. Over a 6-month period, annexin V binding by leukocytes was determined daily using flow cytometry and FITC-labeled annexin V in 33 postoperative patients with severe sepsis or septic shock during their intensive care unit stay. The percentage of annexin V binding neutrophils, monocytes, and lymphocytes was significantly lower, and G-CSF plasma concentrations were higher in patients than in controls on most days. Nine, 19, and 18 peaks in neutrophil, monocyte, and lymphocyte counts (increase of >/=30% within 2 days, followed by a decrease of >/=30% within 2 days) occurred in 6, 11, and 16 patients. During leukocyte peaks, the absolute numbers of annexin V binding neutrophils, monocytes, and lymphocytes paralleled those of neutrophil, monocyte, and lymphocyte numbers. However, the percentage of annexin V binding neutrophils, monocytes, and lymphocytes did not differ significantly from one day to another. Increased G-CSF serum concentrations preceded neutrophil and monocyte peaks. In conclusion, apoptosis of leukocytes is lowered during severe sepsis and septic shock in critically ill patients. Moreover, the degree of apoptosis does not increase during transient leukocytosis. G-CSF might contribute to the low degree of apoptosis of neutrophils and monocytes in those patients.

Annexin A5↗

Antibody responses after vaccination and disease against leukocytosis promoting factor, filamentous hemagglutinin, lipopolysaccharide and a protein binding to complement-fixing antibodies induced during whooping cough.

The serum antibody responses of vaccinated children and whooping cough patients to the highly purified Bordetella pertussis antigens, leukocytosis-promoting factor (LPF), lipopolysaccharide (LPS), a protein binding to complement-fixing antibodies induced during whooping cough (PBCA) and to a partly purified filamentous hemagglutinin fraction (FHA) were analysed in enzyme-linked immunosorbent assay. Of the IgG antibodies, those to FHA and LPS were often persistent both after infection and vaccination. The mean titers were about six to ten times higher after disease than after vaccination in corresponding age groups. IgG antibodies to LPF were frequently detected in high titers in patients (mean arbitrary units = 1723), but seldom in low titers (mean units = 20), after vaccination. IgG antibodies to PBCA disappeared some years after vaccination. IgM antibodies to PBCA, FHA and LPS were present in almost 100% after vaccination and disease. IgM antibodies to LPF were detected in 23% of the vaccinated and in 83% of the patients. The respective mean IgM units to PBCA, FHA, LPS and LPF were 14, 13, 16 and 134 times higher in patients than in vaccinated children. None of the vaccinated children and 20% of the patients had IgA antibodies to LPF. No pronounced differences in the percentage of the respective IgA responses to PBCA, the FHA fraction and LPS were found between the two groups. The striking differences in the immune response of vaccinated children and patients were to LPF. Since whooping cough protects better than vaccination against B. pertussis infection, the present study indicates that immunogenic LPF should be included in an acellular vaccine. Also addition of FHA, PBCA and possibly even of LPS, if it can be prepared in an immunogenic and atoxic form, might be necessary in order to prepare a highly effective acellular vaccine.

Adolescent↗