Human neutrophil lipocalin (HNL) and myeloperoxidase (MPO). Studies of lung lavage fluid and lung tissue

Abstract

Myeloperoxidase (MPO) and human neutrophil lipocalin (HNL) are proteins which are stored in neutrophil granulocytes, in the primary and secondary granules, respectively. These granules or their contents of MPO and HNL are secreted upon activation of the cells, and measurement of these soluble markers in biological fluids, such as bronchoalveolar lavage (BAL), has been proposed to mirror the degree of neutrophil activity in the tissue. We conducted a BAL study in 10 healthy volunteers, with the aim to evaluate the intra-individual variability of the concentration of HNL and MPO recovered in sequential aspirations, during a time period when the concentrations of HNL and MPO in BAL fluids were considered to have equilibrated with those in the underlying tissues. The concentrations of HNL were less variable than those of MPO (coefficients of variability 0.33 +/- 0.07 vs. 0.92 +/- 0.28; P = 0.01), suggesting HNL to be a more useful marker of neutrophil activity within the airspace. The specificity of HNL as a selective index of neutrophil cells was confirmed by means of immunohistochemical staining of uninvolved lung tissue specimens obtained from patients referred to pulmonectomy due to carcinoma. While HNL was located only to intracellular spaces of neutrophils, MPO was in addition located to other cells as well. We speculate that the dynamic changes of pressure across the membranes and flow of solutes during a lavage process might mobilize particulate matter and adherent cells, some of which may be loaded with MPO, and that this may introduce larger variability in the recovery of MPO than of HNL. We conclude that using HNL as a soluble indicator of neutrophil presence is more feasible than using MPO.