Mesenchymal Cells Neighboring the Acini

Myofibroblasts and Fibroblasts

Mesenchymal cells neighboring the acini were morphologically classified into two broad types: myofibroblasts and fibroblasts. Myofibroblasts often had a folded nucleus and many micropinocytic vesicles (fig. 1). Organelles such as the Golgi complex and the endoplasmic reticulum were developed to various degrees. Intracytoplasmic filaments with focal densities and plasmalemmal densities were often found. Occasionally, basal-lamina-like fragments were formed. In contrast, the fibroblasts had few micropinocytic vesicles, no intra-cytoplasmic filaments, and no basal lamina. At the advanced stage of periacinar

Table 1. The relation between periacinar collagenization and myofibroblasts and fibroblasts

Stage

Periacinar collagenization

Mesenchymal cells Myofibroblasts

Fibroblasts

I

None

II

Very slight

+

III

Slight

+

+

collagenization, the myofibroblasts possessed well-developed endoplasmic reticula and Golgi complexes, and were similar to developed fibroblasts.

The ratio of these two types of mesenchymal cells was different at each stage of the initial periacinar collagenization, which was divided into three stages (table 1). At the stage of no microscopic periacinar collagenization (stage I), no or few myofibroblasts or fibroblasts were found around the acini. Some per-icytes and a few collagen fibrils were observed in the interstitium. The morphology of pericytes was often similar to that of myofibroblasts, but they had much more micropinocytic vesicles than myofibroblasts, and had complete basal lamina, like the endothelia of small vessels. When the microscopic periacinar collagenization was very slight (stage II), the myofibroblasts were the only mesenchymal cells neighboring the acini. Numerous fine filaments, 8-15 nm in diameter, were found between the myofibroblasts and collagen fibrils (fig. 2). At the stage of slight microscopic periacinar collagenization (stage III), in which a few collagen fibers were found around the acini, both myofibroblasts and fibroblasts were more spindle-shaped and interlaced with many collagen fibrils close to the basal lamina of the acinar cells. It was clarified that myo-fibroblasts preceded fibroblasts as mesenchymal cells neighboring the acini, and that the morphological changes of periacinar mesenchymal cells were apparently correlated with the volume of collagen fibers at the initial stage of periacinar collagenization, regardless of alcohol intake.

Many investigators have also morphologically and immunohistochemi-cally demonstrated the characteristics of the mesenchymal cells neighboring the acinar cells using cells isolated and cultured in vitro. The presence of myofibroblasts in the pancreas is now widely accepted [26-28].

Role of Periacinar Myofibroblasts

Our electron-microscope investigation showed the important role of myofibroblasts in pancreatic fibrosis. The fine filaments (8-15 nm in diameter)

Fig. 2. Collagen fibrils between a myofibroblast (M) and an acinar cell (A) from a 73-year-old male with chronic alcoholism. Note the presence of many fine filaments, which measure 8-15 nm in diameter, between the myofibroblast (M) and collagen fibrils (C), and many micropinocytic vesicles in the cytoplasmic surface of the myofibroblast. Uranyl acetate, lead citrate and tannic acid stain. From [10] with permission.

Fig. 2. Collagen fibrils between a myofibroblast (M) and an acinar cell (A) from a 73-year-old male with chronic alcoholism. Note the presence of many fine filaments, which measure 8-15 nm in diameter, between the myofibroblast (M) and collagen fibrils (C), and many micropinocytic vesicles in the cytoplasmic surface of the myofibroblast. Uranyl acetate, lead citrate and tannic acid stain. From [10] with permission.

between myofibroblasts and collagen fibrils are considered to be collagen filaments, based on their diameter and location. The presence of collagen filaments around the myofibroblasts might indicate that myofibroblasts produce collagen filaments and fibers. Our investigation also revealed that myofibroblasts, not fibroblasts, play an important role as periacinar mesenchymal cells, and contribute strongly to the initial stage of periacinar collagenization. At that time, the existence of myofibroblasts in pancreas was not acknowledged by many investigators, but Apte et al. successfully isolated, from rat pancreatic tissue, stellate shaped cells which transformed into myofibroblast-like cells [27]. Based on the results of our investigation, it was suggested that alcohol has an effect on the initial stage of periacinar collagenization in intralobular sclerosis through the activation of myofibroblasts. The myofibroblasts around the acini were sometimes difficult to distinguish morphologically from pericytes or the endothelium in neoformed small vessels. Morphological similarities between myofibroblasts and fibroblasts were also observed at the stage preceding periacinar collagenization. This is inevitable because these cells were considered to be derived from the same stem cells [28].

Fig. 3. Degenerative acinar cells from a 59-year-old male with chronic alcoholism. Note the presence of many lysosomes and lipid droplets in the acinar cells. Uranyl acetate, lead citrate and tannic acid stain. From [10] with permission.

It was also reported from a histological investigation using a-SMA immunoreacitivity that the incomplete obstruction of the main pancreatic duct caused the onset of interlobular fibrosis [29]. The distribution of myofibroblasts in both periacinar and perilobular areas might provide a clue to resolve the mechanism of the three different types of pancreatic fibrosis in terms of pathogenesis.

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