Plasma lactoferrin reflects granulocyte activation in vivo

Abstract

N-formyl-met-leu-phe (FMLP) causes polymorphonuclear leukocytes (PMN) to secrete and become 'sticky' in vitro. We related these events to in vivo FMLP-induced neutropenia. FMLP was intravenously administered to anesthetized rabbits in doses ranging from 0.01 μg to 1.0 μg. Controls received phosphate-buffered saline (PBS), the diluent for FMLP. Blood pressure, respiratory rate, and arterial PO2 were monitored. High and intermediate doses of FMLP caused a dramatic but transient decrease in blood pressure and an increase in respiratory rate. Prior to FMLP infusion, plasma lactoferrin level was 6.4 ± 4.1 μg/ml, and the absolute granulocyte account (AGC) was 2008 ± 1229 (mean ± SD). There was a positive linear correlation between AGC and plasma lactoferrin level prior to injection of FMLP (R2 = 0.74, p < 0.01). At 1 min after FMLP injection, the percent change in AGC decreased as an exponential function of dose to as low as 10% of baseline (R2 = 0.86, p = 0.002) and plasma concentration of lactoferrin increased as an exponential function of dose to as high as 30 μg/ml (R2 = 0.84, p = 0.006). Thus, FMLP-induced neutropenia is associated with increased levels of plasma lactoferrin, suggesting that PMN are induced to degranulate in vivo.