Figure 2.

Interacting effects of hemolysis, heme-oxygenase-1 (HO-1) induction, and neutrophil mobilization, on neutrophil oxidative burst. (A) Working model of the interactions between hemolysis, HO-1 induction, and neutrophil oxidative burst. Hemolysis has three interacting effects: stimulating the oxidative burst of mature neutrophils; inducing HO-1 expression in neutrophil progenitors in bone marrow (BM) which leads to impaired oxidative burst capacity during neutrophil maturation; and mobilization of neutrophils from BM to the blood. (B) Interaction between measured carboxyhemoglobin % (COHb, an indicator of hemolysis and HO-1 activity), neutrophil count in peripheral blood, and PMA-stimulated oxidative burst (rhodamine MFI) of neutrophils in patients with sickle cell disease. The fitted surface shows the predicted oxidative burst response (using a generalized linear model), and overlying black dots show individual patient data (n=20). (C) Predicted change in PMA-stimulated oxidative burst with neutrophil count at different levels of COHb [(representing the 25^th (dashed line), 50^th (dotted line), and 75^th centiles (dash-dot line) in subjects with sickle cell disease)]. The horizontal line represents the lowest value observed in control subjects.