Abstract

The CD11b (Mol) molecule is a member of a family of surface glycoproteins that are essential for adhesion-dependent granulocyte functions. Brief exposure of granulocytes to human granulocyte- macrophage colony-stimulating factor (GM-CSF) in vitro increases the surface expression of CD11b and increases granulocyte adhesiveness. To assess the possible in vivo significance of these observations we studied the effect of GM-CSF on CD11b, CD11a (LFA-1), and CD11c (gp 150, 95) expression on granulocytes from nine adult patients with sarcoma who were receiving GM-CSF as part of a phase I trial. GM-CSF was administered as a continuous infusion at a dose of 32 or 64 micrograms/kg/d. Granulocyte CD11b, CD11a, and CD11c expression was determined by indirect immunofluorescence staining of whole blood, thereby minimizing in vitro manipulation. A transient leukopenia developed within 15 minutes of initiation of GM-CSF treatment that was associated with a marked increase in the surface antigen density of CD11b. A mean 1.7-fold increase (P = .001) in the percentage of CD11b- positive granulocytes and a mean 2.1-fold increase (P = .002) in CD11b surface antigen density was noted after 12 hours of treatment. No change in CD11a or CD11c expression was observed over the first 12 hours. The level of CD11b expression was followed in six patients for up to 5 days of treatment with GM-CSF. Compared with the 12-hour value, three of six patients showed a subsequent decrease in CD11b expression, two remained constant, and one showed a continued increase in CD11b surface density. Fluorescence-activated cell sorting of granulocytes into high- and low-density CD11b-positive groups revealed a preponderance of immature myeloid forms in the low-density CD11b fraction, which suggests that the late decrease in CD11b expression in some patients may be related to a greater proportion of circulating immature myeloid forms in the peripheral blood. This study suggests that GM-CSF administered as a continuous infusion rapidly upregulates the expression of granulocyte CD11b in vivo. The influence of this phenomenon on in vivo granulocyte aggregation may be clinically relevant with regard to the toxicity of GM-CSF and deserves further investigation.

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