Regulation of intracellular lysosomal movements by the cytoskeletal system in rat alveolar macrophages.

Abstract

Saltatory intracellular lysosomal movements were enhanced by both fluidphase pinocytosis (horseradish peroxidase; HRP) and adsorptive pinocytosis (peroxidase anti-peroxidase; PAP) in cultured rat alveolar macrophages. To elucidate the role of cytoskeletal elements in the regulatory mechanism of lysosomal movements related to the autophagy and heterophagy, the effects of actin filament destabilizers (cytochalasin B, D) and antimicrotubular drugs (colchicine, nocodazole) on the lysosomal movement induced adsorptive pinocytosis of PAP were investigated by cytochemical electron microscopy.In the cultured alveolar macrophages, the pinocytosis of PAP promoted lysosomal movements and the extension of nematolysosomes (thread-like lysosomes) within the cytoplasm. The actin filament destabilizers inhibited these lysosomal movements and forming process of nematolysosomes, while the drugs had little or no inhibitory effect on pinocytosis of PAP. The antimicrotubular drugs also had an inhibitory effect on the appearance of nematolysosomes. Moreover, these drugs led to another type of lysosomal transformation, i.e., wrapping lysosomes which are thought to be one process of autophagy.The present study using actin filament destabilizers and antimicrotubular drugs clarifies two distinct types of lysosomal transformations, which are nematolysosomes and wrapping lysosomes. It is suggested that cytoskeletal elements play an important role in regulating the movement and transformation of lysosomes in the macrophages.Lysosomes are regarded as an intracellular digestive system which actively moves through the cytoplasm. This organelle is polymorphic in shape, size and internal structure. In particular, the polymorphic structure of lysosomes is seen most typically where intracytoplasmic digestion actively occurs, e.g., in macrophages (14,30,36,37,44,45,49,50). This polymorphism seems to be the result of active intracellular movements associated with lysosomal functions in heterophagy and/or autophagy (22, 23,34,36,37,49,50). However, little is known about the regulatory mechanism of '

In situ and in vitro morphological evidence for the interaction of actin filaments with lysosomes in rat alveolar macrophages.

“…In the matter of microtubules, the close association of microtubules with lysosomes in macrophages was recently shown in the articles described by Swanson et al (25,26) and in our previous study (3).…”

“…In the previous report, we showed that lysosomal movements and transformations were greatly affected by actin filament destabilizers and antimicrotubular drugs (3). To confirm this circumstantial evidence suggesting an important role of cytoskeletal elements in the regulation of lysosomal movements, the direct morphological interaction of actin filaments with lysosomes in rat alveolar macrophages were examined by several electron microscopic techniques.…”

“…The antimicrotubular drugs induced another transformation of lysosomes, i.e., wrapping lysosomes, during autophagy (3,19). These results suggested that various lysosomal movements seemed to be caused by the modulation combined by cytoskeletal elements such as actin filaments and microtubules.…”

“…In some of the cultured cells, intracellular lysosomal movements were induced by adsorptive pinocytosis of peroxidase anti-peroxidase (PAP, 0.25 mg/ml in Medium 199) as described previously (3). Bovine serum albumin (BSA)-conjugated colloidal gold which was prepared according to the method described by Geoffroy et al (9) was also used as a pinocytic marker to label lysosomes.…”

cAMP-mediated inhibition of intracellular particle movement and actin reorganization in Dictyostelium.

“…The relationship of particle movement and the cytoskeleton has long been a focus of investigation (e.g., 2,11,28,29). Therefore, we tested whether parallel cytoskeletal events accompanied the depression in particle movement and cellular motility immediately after cAMP addition.…”