Arch. histol. jap., Vol. 40, No. 4 (1977) p. 305-320 Department of Internal Medicine (Prof. M. MATSUOKA) andDepartment of Anatomy (Prof. T. FUJITA), Niigata University School of Medicine, Niigata, Japan Megakaryocyte
and
Platelet
Microscope Toshio
Formation: Study
in Mouse
IHZUMI, Akira
A Scanning
Electron
Spleen
HATTORI, Masayoshi and Masaki MUTO
SANADA
Received April 20, 1977
Summary. Mouse spleen was examined by scanning electron microscopy after perfusion fixation and cryofracture. Megakaryocytes are recognized usually in the splenic cord near the sinus and postsinal venules but rarely in their lumen. They are usually fixed to the reticulum cells and sometimes both cells are connected to each other by cytoplasmic interdigitations. Immature megakaryocytes are round but mature ones are irregular in shape with many cytoplasmic protrusions. The cell surface reveals small pores and many microprocesses of two types: Type I microprocesses are blebs known to be involved in platelet liberation, while the significance of type II or villous microprocesses remains unknown. Surface pores represent the orifices of the platelet demarcation membrane system (DMS) in the cytoplasm. On the fracture surfaces of the cell, the DMS is recognized as a network of furrows and its development is confirmed to be initiated by invagination of the plasma membrane. Individual platelets formed by developing DMS become seined spheroid in shape. Platelet release occurs in four different modes: 1) After the DMS has divided individual platelets in the intermediate zone of megakaryocyte, it invades the ectoplasm encircling small surface areas. Some ectoplasmic pieces thus formed are liberated from the cell like a cork being withdrawn from a bottle. Through these ectoplasmic defects the interior platelets are released either in masses or in beaded ribbons. Individual platelets liberated in the splenic cord migrate into the sinus lumen through the intracytoplasmic fenestration of the endothelium. 2) Megakaryocytes project larger pseudopods into the sinus lumen, which become fragmented into platelets. 3) Megakaryocytes themselves enter the circulation and release platelets in remote organs such as the lung. 4) The megakaryocytes project small ectoplasmic blebs (type I microprocesses) into the sinus lumen and then detach them. By this process, as well as by the fragmentation of the ectoplasm above mentioned, megakaryocytes may produce platelets lacking in organelles. Since WRIGHT(1914) described that the megakaryocyte is the mother cell of blood platelets, many investigations have been made on this cell by means of light microscopy, phase contrast cinematography, transmission electron microscopy (TEM) and recently by means of scanning electron microscopy (SEM). In these studies, the areas of inquiry have been how and where the megakaryocyte releases the platelets and, since YAMADA(1957) found the platelet demarcation membrane system (DMS), how the system is formed in the cell. Various observations on the origin of the DMS have been made: YAMADA(1957) reported that the system was formed by the coalescence of special vesicles which were distinctly different from the elements of smooth endoplasmic reticulum. Some authors regarded the DMS as a derivative (SCHULTZ, 1966) or a specialization (HAN and BAKER,1964) of endoplasmic reticulum, whereas 305
306
T. IHZUMI et al.:
others thought that its formation was initiated by invagination of the plasma membrane (BEHNKE, 1968; MACPHERSON, 1972). YAMADA(1957) proposed that the slits of the DMS in the mature magakaryocytes extended by their coalescence and subdivided small cytoplasmic areas (platelet zones), each of which developed into platelets. Although YAMADAdid not mention the possible mechanism of the release of platelets thus separated, later researchers suggested various modes of platelet release. Some observed that whole megakaryocytes were simultaneously fragmented into platelets (ALBRECHT,1957; KOSAKI, 1974). Others described that individual platelets were liberated one after another from the pseudopods of the megakaryocyte (WEISS, 1970; KEYSERLINGK and ALBRECHT, 1968; BEHNKE, 1969). Intrasinal occurence of platelet release has been commonly accepted, but BEHNKE (1969) considered that both intra- and extrasinal platelet liberation was possible. The extrasinal platelet release has remained to be confirmed and it is also obscure as to how platelets born in the splenic cord could migrate into the sinus lumen. TANAKA(1972) described in his textbook that ectoplasmic bleb-like projections lacking in organelles (type I microprocesses in the present paper) are released as a kind of platelet into sinus lumen, although DE BRYUN(1964) had regarded them as a type of apocrine secretion. In accordance with the view of TANAKA,we sometimes encounter platelets lacking organelles in the peripheral blood, although their significance is unknown. We observed megakaryocytes by SEM in various stages of maturation in the cryofractured mouse spleen in order to clarify the above problems. This material was chosen because the mouse is known to have numerous megakaryocytes in the spleen. Materials and Methods Twenty ICR mice, weghing about 20g, were used in this study. Under anesthesia by ethyl-ether inhalation, the abdominal and pleural cavities were opened to expose the heart and spleen. A polyethylene tube was inserted into the left ventricle of the heart; and perfusion was made through the tube first with 200ml of saline to wash the vascular bed and then with 100ml of 1% glutaraldehyde (in 0.1M phosphate buffer, pH 7.4) to fix the tissue. The portal vein was cut down to drain the blood and perfusate. The perfused and fixed spleen was taken out and immediately cut into small pieces about 1mm3. These specimens were kept in the same fixative for 2hrs, and then transferred to a solution of 2% glycine, 2% glutamate and 2% sucrose and a 2% aqueous solution of tannic acid and finally to 2% osmium tetroxide according to the method of MURAKAMI (1974). The specimens were dehydrated by acetone, transferred to isoamylacetate, and freeze-cracked in liquid nitrogen by the method of TOKUNAGAet al. (1974). The cracked specimens were dried by the CO2 critical point method, evaporated with gold palladium, and observed in a Hitachi HFS-2 field emission SEM with an accelerating voltage of 10kV. Small specimens of the perfusion-fixed spleen were post-fixed in OsO4 and simultaneously processed for TEM according to the conventional method. The thin sections were doubly stained with uranium acetate and Sato's lead staining (SATO, 1968) and examined in a Hitachi HU 125-DS electron microscope.
Megakaryocyte and Platelet Formation
307
Observations General structure
of megakaryocyte
The megakaryocytes, easily identified by their unusually large size, were frequently found in the splenic cord but rarely in the sinus and venule lumen. In the splenic cord, many megakaryocytes were located near the sinus and venule wall; some actually attached to their wall. Their gross contour was generally spherical or ovoid (Fig. 1) and occasionally irregular (Fig. 2). The diameter of the megakaryocytes
ranged
from
parenchymal size
19
tissue
should
be
to
42μ.
during
between
If
the
fixation 20
and
44μ.
shrinkage and
rate(-64%
drying
is taken
Megakaryocytes
by into were
TOSHIMA,
1976)
consideration, usually
the
of
the
actual
surrounded
and
partly tightly attached by reticulum cells. When the cell body of the megakaryocyte was encircled by reticulum cell processes, the former was sometimes constricted into a dumb-bell shape (Fig. 2). A close association was recognized between the interdigitated portions of both types of cells (Fig. 4). The cell surface was smooth or slightly uneven, showing some pores and microprocesses (Fig. 1, 2, 5). The latter were divided into two types: Type I, rounded ones
Fig. 1. Spherical megakaryocyte with its exposed nucleus (N). The platelet demarcation membrane system (*) shows mainly tubular structures in the cytoplasm. Microprocesses (thin
arrows)
and
pores
(thick
arrow)
are
seen
on
the
cell
surface
(**).
×9,400
308
T. IHZUMI et al.:
Fig. 2. Mature megakaryocyte. Pores have developed at multiple sites on the cell surface (**). Well developed DMS is seen in the fractured portion of the cell (*). The cell is constricted
by
reticulum
fibers
(arrow).
×3,200
Fig. 3. High magnification of a part of Figure 2, showing both fracture surface (*) and cell surface (**). A pore is connected with the demarcation membrane (thin arrow). A microprocess is found in a pore and some others stand the margin of the pores (thick arrow). The mage-like interior of the megakaryocyte is seen through a large complex pore (paired arrows). ×12,300
Megakaryocyte with
or
without
processes
a thin
correspond
processes
were
neck; to
villous
their
the
maximum
blebs
in
and Platelet
Formation
thickness
hitherto
was
described
appearance,
about
in
1.6μ
309
long
about
TEM
1.6μ.
These
studies.
and
0.3μ
Type thick
microII
(Fig.
micro5).
No
clear description seems to have been previously made of this type. The frequency and the distribution of these microprocesses differed from cell to cell; their distribution was sometimes localized to a limited section on the surface. Some megakaryocytes possessed both types of processes, while others only one type (Fig. 2). The
pores
appeared
generally
round
(0.04-0.6μ
in
diameter)
but
occasionally
ir-
regular, elongate or slit-like; a complex form consisting of a few smaller pores was sometimes encountered. When the pores were large enough, a maze-like internal structure of the megakaryocyte could be recognized through them. Occasionally single villous microprocesses (type II) stood on the margin of the pores; a few processes were also noted projecting from the pores (Fig. 3). Viewing up
to
20μ
Some
were
the length)
fracture were
tubular,
surface, observed
showing
numerous to
be
round
either
holes
furrows
and
scattered
or
when
crossly
slits grouped
cut
(about
(0.2-0.3μ in 0.2μ
width
the
and
cytoplasm. in
diameter)
(Fig. 1, 2, 3, 5). On the basis of their distribution and dimension, this intracellular space system was considered to correspond to the DMS found in thin sections. In appropriate fracture surfaces which included the cavities of the surface pores, the plasma membrane was confirmed to continue into the demarcation membrane; the pores were the orifices of DMS (Fig. 3). On a favorable fracture surface, a characteristically lobulated nucleus was found in the central part of the cell (Fig. 1, 5). Its surface was smooth, showing occasional nuclear pores. Near the nucleus, Golgi apparatus could be recognized as lamellar slits which
were
narrower
(0.07μ)
than
the
demarcation
slits
above
mentioned.
Apparent
Golgi vesicles often contained small granules. Larger granules (future platelet granules) and their sacs were also found in the cytoplasm as spherical bodies or cavities, 0.2μ
in
diameter
(Fig.
Fig. 4. Fracture surface of the plasma membrane seen at the cell periphery
3, 5).
of immature megakaryocyte (M) and reticulum cell (R). Invagination (single arrow) and tubular elements (paired arrows) of the DMS are of the megakaryocyte. Note cytoplasmic interdigitation between the megakaryocyte
and
reticulum
cell.
×6,200
310
T. IHZUMI et al.:
The TEM observation by BEHNKE(1968) and the present study indicate that the DMS first appears at the cell surface as plasma membrane invagination in immature megakaryocytes. The DMS then develops into a large network in the intermediate zone. This network later spreads to occupy almost the entire cytoplasm just prior to platelet release. The amount and distribution of the DMS in the cytoplasm as observed by SEM of fractured specimens, therefore, indicate the maturation degree of the cells. The SEM findings in immature and mature megakaryocytes thus identified are described below. Immature
megakaryocytes
Immature megakaryocytes were generally spherical in gross contour (Fig. 1). Both types of surface microprocesses were found. The villous ones (type II) were relatively few but they were occasionally densely gathered in a limited area. The pores
were
generally
round
(0.1-0.4μ
in
diameter)
and
often
gathered
in
groups.
The DMS in this stage was mainly represented by tubular channels which occurred only near the plasma membrane (Fig. 4); this was confirmed also by the present observation of thin sections by TEM. Mature megakaryocytes Mature megakaryocytes tended to be more irregular in shape than the imma-
Fig. 5. Mature megakaryocyte surface (**). Two types of the
in the splenic cord, showing cell surface (*) and fracture surface microprocesses are observed: Type I micropocesses
(blebs) are indicated by thick arrows, while type II or villous microprocesses by thin arrows. In the cell center, platelet zones (P) encircled by well developed DMS and some cytoplasmic granules are discernible. This cell attaches to the sinus wall, projecting its bleds into the sinus
lumen
(S).
N
nucleus.
×6,200
Megakaryocyte
and Platelet
Formation
311
Fig. 6. Megakaryocyte projecting its blebs into the sinus lumen (S), some of which have been detached
Fig.
7.
from
Fracture
the
cell.
surface zones,
which
They
may
of mature are
seen
be
platelets
without
organelles
megakaryocyte.
Well
as
(arrows).
spheroid
bodies
(arrow).
developed
×14,000
DMS forms
×11,900
platelet
312
T. IHZUMI et al.:
Fig.
8.
Irregular
shaped,
platelet
(arrows),
which
releasing may
Fig. 9. Part of megakaryocyte surface. into platelets zones without organelles,
be
megakaryocyte detached
as
with
platelets.
many
tear-drop
processes
×4,500
Small surface areas are divided by channels of DMS some of which may detach from the megakaryocyte. ×25,000
Megakaryocyte
ture
ones
rence on
the
surface
of
due to the constriction large
protrusions.
surface; pores
although were
increased
and Platelet
of the bodies Many
they
by reticular
processes
were in
of both
densely
number
Formation
and
cell processes types
gathered size,
313
were
in some
measuring
up
and
generally 0.8μ
occur-
scattered
portions. to
the The
in
cell
diameter.
They were generally round in shape. Occasionally, they accumulated at multiple sites on the cell surface. Complex pores now appeared at this stage. The spaces of the DMS became numerous at the intermediate zone of the cytoplasm, forming a complicated network of slits with a sponge-like appearance. On the fracture surface they appeared mostly saccular or irregular in shape (Fig. 3. 5). The cytoplasmic areas encircled by them (so called platelet zones) were not always discoid but often rounded
in
shape.
processes (Fig. 7).
They
measured
Some mature
about
1.6μ
in
megakaryocytes
diameter
and
often
possessed
were observed migrating
spiny
into the
Fig. 10. Fracture suface of a platelet releasing megakaryocyte. Numerous platelet zones (P) are seen in the intermediate cell portion. The ectoplasm (*) is discontinuous at two sites (arrows), from where the platelet zones are exposed and ejected to the extracellular space. N
nucleus.
×5,600
314
T. IHZUMI et al.:
lumen of the sinus and the postsinal venule, i.e., the pulp vein portion close to the sinus through their walls; a few cells had invaded the sinus lumen. Platelet
releasing
megakaryocytes
The megakaryocytes under platelet liberation were irregular in shape: their surface was characteristically wavy and intricate with many cytoplasmic protrusions (Fig. 8, 10). The previously round pores now have elongated into irregular spaces. Finally they encircled small surface areas or platelet zones in a manner similar to those of the DMS in the interior of the cytoplasm (Fig. 9). The DMS then invaded the ectoplasm and the platelet zones were sometimes elevated as small cytoplasmic protrusions (Fig. 10.). Some of them detached from the megakaryocyte like a cork being withdrawn from a bottle. Besides, bleb-like microprocesses occured here and there on the cell surface. Some of the blebs became larger and developed into a teardrop shape which was attached to the megakaryocyte only by a thin neck (Fig. 8). In the lumen of the sinus and of the postsinal venule, two types of protrusions of megakaryocytes were found: the smaller type showed shapes like pearl beads or
Fig.
11.
karyocyte
Beaded in
the
(thin arrows) venule
lumen.
and bunched The
yare
(thick arrows) believed
to
be
cytoplasmic separated
protrusions into
platelets.
of the mega×2,200
Megakaryocyte
and Platelet
Formation
315
Fig. 12. A platelet (arrow) passing the sinus wall (S) through an intacellular fenestration of the endothelium. Two platelets are further shown: one at the outer surface of the sinus wall and
the
other
in
the
sinus
lumen.
×18,000
bunches of grapes similar to the protrusions of the platelet zones in the splenic cord (Fig. 11), and the larger type had pseudopods possessing round (type I) and villous (type II) microprocesses as well as pores. Near these pseudopods some single platelets were scattered. By TEM as well as SEM, the blebs lacking in organelles were confirmed to be projected into the sinus lumen through fenestrations of the endothelium; and some of them most probably were being detached from the megakaryocytes (Fig. 5, 6). Platelet
migration
into the sinus lumen
A number of separate platelets were found in the splenic cord and also on the outer surface of the sinus wall. Several platelets were in the sinus wall and some of them were confirmed to be located not between but in the endothelial cells. Furthermore, some platelets were observed on the inner surface of the sinus wall (Fig. 12). Thus it seems most probable that the platelets born in the cordal tissue may migrate through the intracytoplasmic fenestrations of the endothelial cells. Residual
megakaryocytes
Residual megakaryocytes were recognized as smaller cells with a strikingly scanty cytoplasm having nuclei similar in dimension to the mature megakaryocytes. The surface was characteristically undulated in a reticular pattern. This structure presumably represented the residual DMS.
316
T. IHZUMI et al.
Discussion Demarcation
membrane
system
In his TEM study on mouse spleen megakaryocytes, YAMADA(1957) first observed that the earliest manifestation of DMS was the appearance of vesicles in the intermediate zone of the cytoplasm, that those vesicles developed to a maze-like structure by coalescence, and that finally the DMS of mature megakaryocytes separated numerous platelet zones throughout the intermediate portion of the cytoplasm. As for the origin of the DMS, YAMADA(1957) considered that it was a distinct element differing from the smooth endoplasmic reticulum. Later, DE BRYUNin guinea pig bone marrow and HAN and BAKER(1964) in rat bone marrow reported that the DMS continued to the smooth endoplasmic reticulum. BEHNKE(1968), by TEM, demonstrated that both the DMS and the plasma membrane were similary demonstrated by horse radish peroxidase, thorotrast and ruthenium red. From this observation and, from the fact that a continuity of the DMS to the plasma membrane has been repeatedly reported in mature megakaryocytes (YAMADA,1957; HAN and BAKER,1964; KEYSERLINGK, 1968;BEHNKE,1968), BEHNKE (1968) concluded that the origin of the DMS was plasma membrane, i.e., its formation initiated by an invagination of plasma membrane. In his TEM study using rat bone marrow, MACPHERSON (1971) observed different stages of initial invagination of plasma membrane in very immature cells. By SEM examination of fractured cells, we demonstrated the continuity of the surface pores to DMS in both immature and mature cells as shown in Figures 4 and 3. Furthermore, some villous microprocesses were found to stand on the margin of pores or even in pores as shown in Figure 3. These microprocesses can be reasonably considered to have been pulled into the pores by the invagination of plasma membrane. On the basis of these findings, the present observation supports the conclusion of BEHNKE (1968)and MACPHERSON (1972) onthe origin of the DMS. Concerning the site of the invagination, two observations were reported. BEHNKE (1968) showed that it occurred at multiple sites of the cell membrane, whereas MACPHERSON(1972) hypothesized that it initiated first at a point on a pseudopod and that later it occurred at mulitiple sites. This initiation of the invagination at one particular site was not confirmed in our study. This discrepancy may have resulted from the fact that the megakaryocytes in our observation were probably more mature than those observed by MACPHERSON (1972).Our observation demonstrated that the plasma membrane invagination occurred at several points in relatively immature cells. The invagination later developed at more numerous sites throughout the surface, and they became intricately infolded into the intermediate zone of the cytoplasm. Platelet
zones and platelet
release
As viewed in SEM, the DMS separated cytoplasmic portions and subdivided them progressively until numerous small platelet zones of spined spheroid contour were formed (Fig. 5, 7, 10). These SEM findings confirm the previous observations obtained in thin sections by various investigators. YAMADA(1957) postulated that DMS and organelles, such as granules and mitochondria in the intermedriate zone invaded the outer zone (ectoplasm) and that the DMS was inserted into the cell membrane at the last stage of maturation. Our SEM images showed that DMS invaded the ecto-
Megakaryocyte and Platelet Formation
317
plasm in the platelet releasing megakaryocytes and at some portions the ectoplasm of the megakaryocytes was subdivided into small segments, i.e., "platelets" without organelles. Such development of DMS on the cell surface coincided with our observation that elongate and irregular surface pores coalesced into channels encircling small surface areas corresponding in size and shape to the platelet zones in the cytoplasm. The small surface areas were apparently ejected as shown in Figure 10. This process has not been previously reported. Through the site where the ectoplasm thus became lost, the megakaryocyte porjected its interior platelet zones into the sinus and venule lumen as beads of pearls or bunches of grapes (Fig. 11). Ribbonlike protrusions of megakaryocytes into the sinus lumen have been reported by MUTO (1974) and BECKER(1974) in their SEM observations of rat bone marrow, and by THIERY and BESSIS (1956) in cell culture. Platelets are believed to be liberated by segmentation of this type of process. On the other hand, the grape-like forms found in this study probably correspond to proplatelets (BECKER,1976) which will separate into platelets later. Another mode of platelet separation was that the megakaryocytes projected larger cytoplasmic pseudopods into the sinus or postsinal venule lumen; later, platelets detach from these pseudopods one after another. This mode in which the DMS does not seem to play a major role in platelet release has been described by BEHNKE(1969). The third mode was that the megakaryocytes themselves migrated into the sinus lumen. These megakaryocytes were usually mature but not so far as to liberate platelets. These cells are believed to enter the circulation and release platelets after settling in other organs, as KAUFMANN (1965) demonstrated platelet liberation from megakaroycytes in the lung. Concerning the blebs, their detachment from the megakaryocyte ectoplasm was found in the sinus lumen as shown in Figures 5 and 6. Previonsly, DE BRUYN(1964) observed a similar phenomemon in guinea pig bone marrow but regarded it as an apocrine secretion of megakaryocyte. TANAKA(1372) described it in his textbook as a mode of platelet release. On the other hand, BEHNKE(1969) could not find the blebs in rat bone marrow megakaryocytes fixed by perfusion and considered that the blebs represented a degenerative change produced by incomplete fixation. Our stuby using fixation conditions similar to those of BEHNKEsuggests that the blebs are not degenerative changes but proper cell structures. This descrepancy between BEHNKE's result and ours may possibly be attributed to the difference in species. After being detached, the blebs seem to circulate as a kind of platelet since platelets lacking in organelles are occasionally found in mouse vessels and in human peripheral blood (HATTORI,1967; TANAKA,1972). Their function in comparison is unknown. Platelet
with normal platelets
migration
The course and mechanism of platelet migration from the splenic cord into the sinus lumen has not been clear. In his TEM study in rat bone marrow, BEHNKE (1969) observed migrating platelets through intercellular spaces of the lining cells. By TEM and SEM OGAWA(1975) reported that platelets might pass through the intracellular fenestrations of the sinal endothelial cells. The present study in the mouse spleen clearly demonstrates that platelet migration occurs, at least for the major part, intracellularly (Fig. 12).
318
T. IHZUMI et al.:
Acknowledgment. of Scanning Electron
The authors express their sincere thanks to Mr. K. ADACHI (Laboratory Microscopy of our school) for his technical assistance.
巨 核球 と血 小 板 形 成 機 構-マ
ウ ス脾 臓 の 走 査 電子 顕 微 鏡 に よ る 観 察
飯
泉
俊
雄, 服
真
田
雅
好, 武
部 藤
晃 正
樹
マ ウス脾 臓 を灌 流 固 定, 凍 結 割 断 の の ち, 巨核 球 に つ い て走 査 電 子 顕 微 鏡 に よ る観 察 を 行 な った. 多 くの 巨核 球 は脾 索 内 に存 在 し, 脾 洞 と細 静 脈 の壁 に近 接 し てい た. ま た 稀 に は 洞 内 と細 静 脈 内 に も認 め られ た. 巨核 球 は細 網 細 胞 に よ っ て囲 ま れ,
とき には 両 者 の 胞
体 の鋸 歯 状 結 合 もみ られ た. 巨核 球 の概 形 は, 未 熟 な も のは 円形, 成 熟 す るに 従 って 不 整 形 とな り, 細 胞 表 面 に は大 きな 突起 が み られ た. 巨核 球 の 細 胞 表 面 に は 小孔 と小 突起 が 認 め られ た. 小 突 起 に は2種 類 が 識 別 され, 一 つ は 血 小 板 放 出 に 関 与 す る と考 え られ る球 状 の 突 起 (第 一型) で, 他 は絨 毛 状 の細 長 い 突 起 (第 二 型) で あ るが, 後 者 の 意 義 は 明 らか に され な か った. 細 胞 表 面 の小 孔 は 細 胞 内の 血 小 板 分 離 膜 系 の入 口で あ る こ とが 明 らか に され た. 細 胞 の割 断 面 す な わ ち細 胞 内 に は,
血小 板 分離 膜 系 が 小 溝 とし て認 め られ,
そ
の発 達 が形 質 膜 の細 胞 内へ の 陥 凹 に よ って 始 ま る こ とが確 認 され た. 発 達 し た血 小 板 分 離 膜 系 に よ って 囲 まれ た 血 小 板 小 野 は 金 米 糖 様 の形 を し てい た. 血 小 板 放 出 様 式 につ い ては 四つ の機 序 が 観 察 され た. 1) 血 小 板 分 離 膜 系 が 巨核 球 の 中 間層 に発 達 し, 個 々の 血 小 板小 野 を 形成 した の ち, この分 離 膜 系 が エ ク トプ ラ ズ ム にま で 及 び,
つ い に は細 胞 表 面 を細 区分 す る.
この 部 分 が び んか ら コル ク栓 を ぬ く よ うに して
細 胞 か ら離 れ た の ち, このエ ク トプ ラ ズ ムの 欠 損 部 よ り内部 の血 小 板 が 集 合 して あ るい は リボ ン状 に連 な って放 出 さ れ る. この さい脾 索 で放 出 され た血 小 板 は 洞 壁 の 内皮 細 胞 内 の 小 窓 を 通 って 洞 内 に 流 出 す る. 2) 巨核 球 の大 きな 細 胞 質 偽 足 が洞 内 に突 出 し, 後 に な っ て これ が 個 々 の血 小 板 に 分 離 す る. 3) 巨核 球 が 直 接 血 流 に入 り, 肺 な どで血 小 板 を放 出 す る. 4) 巨核 球 の細 胞 小 突 起 (第 一 型) が 洞 内 に 突 出,
これ が血 小 板 と して離 れ る. こ
の 場 合 は小 器官 の な い血 小 板 が 生 ず る と考 え られ た.
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飯泉 俊 雄 〒951新 潟市旭町1 新 潟大学医学部 第一内科学教室
Dr. Toshio IHZUMI First Department of Internal Medicine Niigata University School of Medicine Asahi-machi 1 Niigata, 951 Japan