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Azurophilic Granules of Human Neutrophilic Leukocytes Are
Deficient in Lysosome-Associated Membrane Proteins but Retain the
Mannose 6-Phosphate Recognition Marker
A.-M. Cieutat,
P. Lobel,
J.T. August,
L. Kjeldsen,
H. Sengeløv,
N. Borregaard, and
D.F. Bainton
From the Department of Pathology, University of California San
Francisco School of Medicine, CA; Center for Advanced Biotechnology and
Medicine and Department of Pharmacology, UMDNJ-Robert Wood Johnson
Medical School, Piscataway, NJ; Granulocyte Research Laboratory,
University Hospital, Copenhagen, Denmark; and the Department of
Pharmacology and Molecular Sciences, The Johns Hopkins University
School of Medicine, Baltimore, MD.
During granulocyte differentiation in the bone marrow
(BM), neutrophilic leukocyte precursors synthesize large amounts of lysosomal enzymes. These enzymes are sequestered into azurophilic storage granules until used days later for digestion of phagocytized microorganisms after leukocyte emigration to inflamed tissues. This
azurophil granule population has previously been defined as a primary
lysosome, ie, a membrane-bound organelle containing acid hydrolases
that have not entered into a digestive event. In this study, azurophil
granules were purified and shown to contain large amounts of mannose
6-phosphate-containing glycoproteins (Man 6-P GP) but little
lysosome-associated membrane proteins (LAMP). In addition, the fine
structural localization of Man 6-P GP and LAMP was investigated at
various stages of maturation in human BM and blood. Man 6-P GP were
present within the azurophilic granules at all stages of maturation and
in typical multivesicular bodies (MVB) as well as in multilaminar
compartments (MLC), identified by their content of concentric arrays of
internal membranes. LAMP was absent in all identified granule
populations, but was consistently found in the membranes of vesicles,
MVB, and MLC. The latter compartment has not been previously described
in this cell type. In conclusion, the azurophilic granules, which
contain an abundance of lysosomal enzymes and Man 6-P GP, lack the LAMP
glycoproteins. By current criteria, they therefore cannot be classified
as lysosomes, but rather may have the functional characteristics of a
regulated secretory granule. Rather, the true lysosomes of the resting
neutrophil are probably the MVB and MLC. Finally, the typical "dense
bodies" or mature lysosomes described in other cells are not present
in resting neutrophils.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 1044-1058
© 1998 by The American Society of Hematology.
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