Neutrophil transfusion therapy has been shown to be efficacious in the support of certain severely neutropenic infected patients and is potentially applicable to large numbers of patients undergoing intensive chemotherapy. Rational use of this therapy requires an understanding of the various factors important in determining the ability of the transfused cells to function in vivo. We propose to study two of these factors -- the effect of short-term storage on neutrophil function and the development of neutrophil alloimmunization. Short-term neutrophil storage studies will include determination of the effect of cell concentration, glucose concentration, pH and temperature on neutrophil integrity. The effect of neutrophil autooxidation on neutrophil viability with storage will be determined by comparing anaerobic and aerobic storage and by examining the effect of adding scavengers of toxic oxygen reduction products. In all of these studies neutrophil function will be assessed in vitro by measuring the ability of the cells to adhere to an endothelial monolayer and to migrate through an endothelial monolayer in reponse to a chemoattractant. The ultimate measure of neutrophil viability will be the in vivo kinetic behavior of the cells, both in blood and at an inflammatory site. The clinical importance of neutrophil alloimmunization will be studied by determining the blood kinetics and skin chamber accumulation of transfused neutrophils in patients receiving neutrophil transfusions and by correlating these results with the occurrence of clinical transfusion reactions and in vitro evidence of circulating antibodies against donor neutrophils. To the latter end we will use standard leukoagglutinin and lymphocytotoxic assays as well as a new quantitative radioimmune assay for antineutrophil antibodies which we are developing in our laboratory. Since in vivo blood and skin chamber kinetic measurements are central to this proposal, continued experiments are also planned to evaluate 111In-oxine as a neutrophil label suitable for quantitative studies.
| Price, T H; Beatty, P G; Corpuz, S R (1987) In vivo inhibition of neutrophil function in the rabbit using monoclonal antibody to CD18. J Immunol 139:4174-7 |
| Harlan, J M; Schwartz, B R; Reidy, M A et al. (1985) Activated neutrophils disrupt endothelial monolayer integrity by an oxygen radical-independent mechanism. Lab Invest 52:141-50 |
| Harlan, J M; Killen, P D; Senecal, F M et al. (1985) The role of neutrophil membrane glycoprotein GP-150 in neutrophil adherence to endothelium in vitro. Blood 66:167-78 |
