Immunocytochemical and cytochemical demonstration of a novel selective lysosomal pathway (SLP) of secretion in the exocrine pancreas.

The intracellular distributions of lysosomal and zymogen granule (ZG) membrane proteins were analyzed in the pancreas exocrine acinar cell by cytochemical and immunocytochemical approaches. A strong signal was observed with acid phosphatase (AcPase) in the trans-Golgi network and condensing vacuoles, whereas mature ZG and acinar lumina were devoid of any detectable reaction. The enzyme appears to exit from the regulated pathway by a shedding process during conversion of condensing vacuoles to mature granules. Trimetaphosphatase (TMPase) shows no reaction in the Golgi apparatus and condensing vacuole but is present in immature granules. The exit from the regulated pathway appears to occur at a later stage of the ZG maturation process. A third lysosomal enzyme, nicotinamide adenine dinucleotide phosphohydrolase (NADPase), was found in the median cisterna of the Golgi stack, was undetectable in condensing vacuoles and ZG, but produced a strong signal in the acinar lumen. Our observations show that only one type of intermediate organelle can explain the transport of that enzyme from the Golgi apparatus to the acinar lumen, and it is represented by a subpopulation of lysosomal bodies (LBs) highly reactive for this enzyme. In parallel, immunocytochemical observations with specific antibodies to GP2, a major protein component of the ZG membrane, have confirmed that most of the GP2 molecules in the acinar lumen do not derive from the ZG compartment but rather are from a subpopulation of highly reactive lysosomal structures. Because both NADPase and GP2 co-localize in specific lysosomal structures, and because these LBs are extruded in the acinar lumen, we conclude that this subpopulation of LBs is involved in selective transport of some lysosomal enzymes from the Golgi apparatus to the acinar lumen. This selective lysosomal pathway of secretion can explain the kinetics of GP2 transport and release from the acinar cell that cannot be explained either by the constitutive or the regulated pathway of secretion.