The major objective of this project has been to study neutrophil function in health and disease. We have shown that a patient congenitally deficient in neutrophil specific granules has major abnormalities in neutrophil function. In normal neutrophils fmet-leu-phe receptors and C3bi receptors (CT3) are present in large amounts in an intracellular pool that cosediments with the specific granules from normal neutrophils on sucrose and Percoll gradients. These are translocated to the cell surface after activation of neurophils resulting in a three fold increase in fmet-leu-phe receptor and CR3. CR3 deficient patients' neutrophils have abnormal chemotaxis, adhesiveness and spreading. Studies comparing peripheral blood and experimental exudate cells in guinea pigs and in man it has shown that there is preferential loss of neutrophil specific granules in the exudate cells. In addition, exudate cells have incresed fmet-leu-phe and C3bi receptor expression. Cytochrome b, found in specific granules, is an important component of the electron transport chain essential for superoxide production. We have shown that neutrophil activation of the respiratory burst requires cytochrome b translocation from an intracellular compartment to the plasma membrane with activation by the calcium ionophore A23187 but not with activation by phorbol esters and fmet-leu-phe. Of 30 patients with chronic granulomatous disease, 11 had cytochrome b deficiency (10 were boys with an X-linked inheritance but interestingly one patient was a girl with probable autosomal recessive inheritance. In other studies of patients with hyper IgE syndrome (recurrent infections) we found that there is decrease catabolism of IgE in these patients.
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