close

Вход

Забыли?

вход по аккаунту

?

Functional homeoplastic grafts of the adrenal gland of newborn rats.

код для вставкиСкачать
FUNCTIONAL HORIEOPLASTIC GRAFTS O F THE:
ADEENAL GLAND O F NlW7BOBN RATS
GEORGE 31. HIGGINB A S D DWIGIIT J. INGLE
Division of Experimental Medicine and Division of Biochemistry,
T h e klago Foziwdatioii, Rochester, Minncaofa
FIVE FIGURES
Autotransplantation of the adrenal gland has been successfully pcrformed on small animals, especially rats (Jaffc, ' 2 6 ;
Poll, 1898; Wymaii and turn Sndeii, '32) and guinea pigs
(Jaffe, '27, '27 a ) , but results have been uniformly uiisuccessful with dogs (Blodinger, I<lebaiioff and Laurens, '26 ;
Johnson and Johnson, '31 ; Oldberg, ,as). Surviving cortical
grafts of adrenal glands of rabbits have been reported (Busch,
Leonard and Wright, '08). For review of the work on transplantation, attention is directed to the articles of Jaffe ('27),
Brittoii ('30), and Loeb ('30).
Homeotransplaiitation of the gland has heeii less successful
than autotransplantation. Schmieden ( '03) reported some
success with rabbits and Jaffe ( ' 2 7 ) , working with rats, reported four successful honieografts out of fifteen trials.
Wyrnan and turn Sudeii ('32) secured successful homeografts
when they exchanged glands between litter mates. They
showed that such homeografts grew equally as well as autografts. I n a large series of homeografts between unrelated
rats of our own strain we (Inglc, IGggins and Nilson, unpublished data) found that only an occasional graft survived
and functioned. I f , on the other hand, glands were cxchangcd
between rats of a strain closely inbred for many generations,
successful homeografts were obtained in a high percentage of
the animals (Iiigle, Iliggiiis and Nilson, unpublished data).
146
146
G. M. IlIGGINY A N i )
I).
J. I N G LE
Lux, Higgins and Mann ('37) attempted to acclimatize
adrenal glands of newborn rats to unrelated adult rats by
growing fragnents of the glands in mcdia containing the body
fluids of the animals selected as hosts. After the tissue had
grown in vitro for 2 weeks, the fragments were grafted to
the adrenalectomized hosts. Successful grafts were obtained
in half of their grafted animals but the data were not convincing that any adaptation of the biologic constituents of the
grafts to those of the hosts was made by 'in vitro' growth of
the glands prior to transplantation. They concluded that successful grafts were owing to similarities between the genetic
constitutions of the donors and those of the hosts rather than
to changes in the tissue during the growth in vitro.
Because of the success of Lux, Higgins and Mann ('37)'
with adrenal glands of newborn rats, v e grafted adrenal
glands of newborn rats to unrelated adults without first grow4 number of attempts have
ing them in tissue culture media. ,
been made to graft embryonic tissues o r tissues of newborn
rats, and a review of these studies was given by May ( ' 3 3 ) .
May has reported successful homeografts of the thyroid and
parathyroid glands of newborn rats, grafted t o the anterior
chamber of the eye. May ('35) likewise grafted the pituitary
bodies of newborn rats and secured successful grafts.
Salmon and Severinghaus ( '36) likewise have reported successful results with homeografts of thyroid glands of newborn rats. Considerably after our work had begun, Rutishauser and Guye ('36) reported that they secured viable
homeografts of the adrenal glands of newborn rats, grafted
t o the renal parenchyma of adult rats. However, percentages
of surviving fiirictional grafts were not included in their
report.
METHODS A S D PROCEDURES
The adrenal glands were removed from newborn rats and
iinmediately placed in the fascia along the femoral veins of
unrelated rats. Ether anesthesia was used, and satisfactory
surgical technic was employed. One group of forty healthy,
male, adult rats, previously adrenalectomized, were used as
GCAFTS O F ADBENAT, GLAKDS IN NEWBORN RATS
147
hosts for grafts. I n another group, consisting of ien healthy
adult, malc rats, the same procedure of grafting was followed
and the same kind of material was grafted but these recipient
animals were not adreualcctomized. Of a third group, consisting of forty-five healthy adult male, previously adrcnalcctomized rats, fifteen received adrenal glands removed from
rats 2 wceks old; fifteen, adrenal glands from animals 1month
old and fifteen, adrenal glaiids from animals 2 months old.
The basic diet of the hosts was our regnlar, standard ration.
Following transplantation, all adrenalectomized rats, that is,
rats of the first and third groups, wcre given 0.8% sodium
chloride in their drinking water and were fed a ration containing 1.5% sodium chloride. Rats of the first and third
groups received the added sodium chloride for 1 week after
transplant ation.
Tn the first group, five rats were killed at intervals in the
first five weeks following grafting, to dctermine the histologic appearance of the graft. a11 other grafted rats of this
group which lived 5 months were explored and the adrenal
tissue ~ 7 a sremoved from the groins. Duration of life of each
animal following removal of the grafted glands was noted.
-4411 grafts were fixed, sectioned and stained with hematoxylin
and eosin, with Illallory’s connective tissue stain, and for
€at and chromaffin reaction. Of the second group of ten adult
rats, two were explored each week for 5 weeks. The grafts
were removed, fixed, sectioned and stained. Concerniiig the
third group, careful data were kept on the length of time the
animals lived and the number of functional grafts recovered.
RESTILTS
Of the forty rats comprising thc first group, twenty-four
survived with functional cortical grafts in the groin. Of
these twenty-four animals7 five were killed during the first
5 weeks after transplanting, as has been said, and nineteen
lived f o r 5 moilths. Each of the iiinctecii had a cluster of
small cortical nodules in the groin closely adjacent t o the
femoral rcssels (fig. 1). The number and size of these nodules
TTIE ANATOMICAL RECORn, VOL
70,
SO
2 AN D
S U P P L X > l I ~ h TNU
2
148
G . M. H I G G I N S A N D 1). J. INGLE
varied. Although ten small glands were grafted, yet the
number recovered m r e r exceeded seven. The size of these
cortical nodules bore some relationship to the number that
regenerated and survived. If three or four survii-ed, the size
of each approximated that of a normal gland but if more
survived, tlie size of each nodule was correspondingly rcdnced.
The total amount of restored cortical tissue was slightly in
excess of the combined weight of the adrenal glands that had
been reniowd from tlie host. Sixteen of the forty animals
x
Fig. 1 Cluster of adrenal glands iu groin of host, 5 months after grafting.
5.
mThic2i werc grafted with glands froin nemhorn r a t s died of
adreiial iiisufliciciicy within 2 to 3 weeks after the salt cow
tent of their drinking water and ration liacl been reduced to
normal. The grafts in these aiiimals had failed to snrvivc.
All nineteen aiiiinals which had viable grafts after 5 months
died within 3 weeks after grafts had been removed from the
groin, indicating that they were functioning and delivering to
the organism the activc cortical principle.
In the scconcl group, the grafts which were renioved at
weekly intervals from tlie p o i n s of rats, which liad not been
GBAFTS O F ADRENAL G I A K D S I N FEWBORN RATS
149
adrenalectomized, were always necrotic. We did not find a
functioning graft in this entire series. Soon after transplantiiig they were infiltrated with leukocytes arid were eitlier resorbed or fibrotic when the last pair of animals were killed
at 5 weeks.
Observations on the third group of adult animals were
continued for 10 weeks after the salt content of their chinking
water and ration had been reduced. There was a considerable
difference in the n u n h e r of animals which survived in each of
the three subgroups. Of the fifteen adult r a t s grafted with
glands reinovecl from unrelated rats 2 nionths old, only one
animal survived for the 10 weeks with a mass of functiouing
cortical tissue. Of the fifteen grafted with glands of rats 1
month old, three were alive, with functioning grafts at 10
weelrs. Of the fiftecn grafted with glands of rats 2 weeks old,
seveii were alive and h r d functional homeografts at 10 weeks.
When contrasting these figures with those given above,
wherein twenty-four of the forty rats grafted with aclrenals of
newborn rats survived with functional grafts, i t seems clear
that age of the transplanted tissue is a factor in the surviral
of a homeograft.
OBSERVATION3 Oh' ?'HE GXA ITS
When a11 adrmal gland of a ncwboru r a t (fig. 2) was removed and grafted to the groin of an adiilt, adrenal
rat, it degeiierated exactly in the manner of an autografted
adult gland ( Pencharz, Olmstecl and Giragossintz, '31).
Kecrosi< first appeared in the center of the gland, the niethdla
TrT'as dcstroyecl and gradually the entire gland, except f o r a
narrow margin of the glomei*ularzone, just below the capsule,
degenerated (fig. 3 ) . During this timc blood vessels penetrated through the capsule from adjacent tissues and polpmorphonuclear leukocytes invaded the necrotic portion. Ruhseyuently, regeneration of new cortical cells took place. This
occurred not only from cells in the persistent portion of the
glomerular zone but from the adjacent capsule as well. This
is in accord with Z~~..emer's
('36) finding that regeneration of
150
G . M. H I G G I N S A N D D. J. IXGLE
GRAFTS O F ADRENAL GLANDS IN NEWBORN BATS
151
zoiia gloinerulosa takes place from the capsule in a normal
adrenal gland.
Regeneration of cortical tissue proceeded from the capsule
and extended into the center of the gland as rapidly a s the
old necrotic tissue was removed. Sections of grafts removcd
a t 3 month showed evidence of considerable regeneration of
cortical tissue, with some necrotic material still persisting
(fig. 4). I n sectioiis of grafts removed 5 months after grafting
were found vascularized masses of cortical tissue cornpri sed
of smaller nodules which had regenerated from tho separate
capsules of the grafted glands (fig. 5).
The characteristic cellular response of the host against a
homeograft occurred in the sixteen aiiirnals which died of
adrenal insufficiency soon after grafting. L:mphocytes infiltrated the gland and foreign body giant cells were commoulv
seen. Here were host reactions against a graft such as Loeb
('30) has described.
COMMEXT
The adrenal gland of the newhorn rat may be grafted to an
iinrelatecl adult r a t and a large percentage of successful functional grafts may survive. Our data show that the results
were someit-hat better than when the technic of tissue culture
was employed to acclimatize the adrenal fragments of one
animal t o the body fluids of the host before grafting. It
seems, therefore, that the succcssful grafts obtained by Lux,
Higgins and Maim ( ' 3 7 ) were owing to the fact that they were
grafting undifferentiated tissue of newborn animals rather
than t o changes which they may have induced in the biologic
differentials of the grafts by growing them in host media.
The chance of securing successful homeografts were
greater when tissues of newborn animals were used. It seems
probable that the age and the degree of differentiation attained by a grafted tissue may be factors which control or
modify its survival and function in the host. I n our experience, the older the donor from which a gland to be grafted
mas removed, the less likely werc we to secure viable grafts.
T H E AA+ATOVICAL RECORD, VOL 70, NO 2 -4ND SUPPLEMENT N O 2
152
G . M. HIGGIKS A N D D. J. IFGLE
Homeografts of an adrenal gland of an adult only occasionally
survived; and yet of forty homeografts of adrenal glands
of newborn animals, 60% survived and functioned. But age
and degree of differentiation of a gland do not constitute all
that is involved in its survival and function. Of forty animals
which receired grafts of adrenal glands of newborn rats, as
stated above, sixteen died. The grafts in all of these had
been destroyed by an aggressive cytologic reaction of the
host. Since all grafts in tliese sixteen hosts were placed along
the femoral vein in exactly the same way as that employed in
placing the grafts in the entire group, failure of the grafts to
survive cannot have been owing to mechanical or to oper nt’ive
procedures. Furthermore, the age of the donors could not
have been cause for failure since all sixteen were grafted
with glands removed from donors, of the same age as those
from whom were taken grafts which survived; that is the
grafts were removed at birth oi- very soon thereafter.
We believe that our failures mere owing to marked biologic
or genetic differences between the donors ancl the hosts. A s
far as we know there was only a remote relationship between
the donors providing the glands and the adults which received
them. All were taken at random from our colony, which is
not closely inbred, but which has been developed from a stock
derived from tlie T i s t a r strain some time ago. It seems
likely that some of the donors may have resembled, genetically
more closely than others, the hosts t o which their aclrenal
glands were grafted. Likewise, others may have been gcnetically urililre tlie liosts. And it is likely that viability of grafts
depended entirely on the degree of the differences that existed
bctsveeii the genetic constitutions of those animals serving
as hosts and those serving as ~lonors. MTe are repeating- this
experiment, using rats of a closely inbred strain in which
brother to sister matings have been made f o r thirty-eight
generations.
GRAFTS O F ADREKAL GLANDS IN NEWBORN BATS
153
CONCLUSIONS
1. Adrenal glands of newborn animals, when grafted to
adult animals, will regenerate, grow and function iii a high
percentage of cases.
2. Regeneration of cortical tissue proceeds from the capsule,
hut medulla does not survive nor regencrate.
3. A considerable pcrccntage of such grafts will not survive. Eost reactions against these grafts resemble the wellknown reactioii against homeografts.
4. The siiccess or failure of a graft probably depends on
the degree of genetic identity between donor and host, .
5. Glands of newborn animals will not regenerate, t o any
extent, in the presence of the host’s ow11 adrenal glands.
6. It seems apparent that another factor in successful
homcotransplantatioii is the age of the donor ; the younger the
donor the greater is the likelihood of survival of the graft.
LITERATURE CITED
BLODINGLR,
1926 Suprarenal transI., H. F:. KLEBANOFF
A N D HBNRYLAUXENS
plantation i n the dog. Am. J. Phjsiol., vol. 76, pp. 151-157.
BRITTOK,
8. W. 1930 Adrenal insuficiency arid related considerations. Physiol.
Rev., vol. 10, pp. 617-682.
Buscn, F. C., T. X. LEONBKD
AND T. WRIGHT 1908 Further results in suprarenal transplantations. J. Am. Ned. Awn., vol. 51, pp. 640-642.
INGLE,
D. J., G. 11. HJGGINS
A N D H. W. NILSON ITnpublished data.
JAFFE,
H. L. 1927 On t h c transplantation of the guinea pig suprarenal and the
functioning of the grafts. 6. Ex?. Xed., vol. 45, pp. 587-594.
1927 a Thc suprarenal gland. Arch. Path., vol. 3, pp. 414-453.
JAFFE, H. L., AND ALEXANDRA
PLAT
SKA 1926 Functioning autoplastic suprar e n d transplants. Proc. Soc. Exp. Biol. and Xed., vol. 23, pp. 528-530.
JOHNSON,
ADELAIDEAND VICTY~R,
JOENSOX
1931 Attempted autotraiisplaiitation
of the adrenal cortex. 9m. J. Phpsitrl., vol. 97, pp. 392-395.
Lorn, L. 1930 Transplantation arid inciividuality. PhysioI. Rev., vol. 10, pp.
547-61 6.
LUX, LYDIA,
G. &f. I I I G G I N S AND F. c. I h X N 19.37 Functional homeografts of
the rat adrenal grown in vitro. Anat. h e . , rol. 70, pp. 29-43.
MAY, R. 11. 1933 Action Tiearlante durable rle la greffe intraoculaire de thyrolde
de raton nouveau-n6 sur le d~veloppeuientdu r a t blaiic ethyroitle.
Arch. de Hiol., T. 44, pp. 149-178.
-____
1935 La greffe brhphoplastique cle l’hypophyse chez le rat. Compt.
rend Soc. de Biol., T. 120, pp. 867-870.
OLDBERG,ERIC 1929 A n attempt t o auto-transplant thc adrenal. Bm. J.
Phgsiol., vol. 91, pp. 275-283.
154
G. M. HIGGINS AND D. J. INGLE
PENCIIARZ,R. I., J. 31. D. OLMSTEDAKD G. GIRAGOSSINTZ1931 The survival of
rats after total and partial adreiialectoniy aiid adrenal transplantation.
Physiol. Zool., vol. 4, pp. 501-514.
POLL,
H. 1898 Ueber das Sehicksal der verpflanzten R’ebenniere. Centralblat. f.
Physiol., Bd. 12, S. 321-326.
RUTISHAUSER, ERWIN, AND PIERREGUYE 1936 La br6phoplastic surr6nalieiine
ehez le rat. Compt. rend. Roc. de biol., T. 121, pp. 1046-1049.
SALMON,
THEODORA
N., AND A. E. SEVERRINGIIAUS
1936 Functional auto- and
homoplastic: thyroid grafts in the rat. Proc. Roc. Exp. Kiol. a n d Ned.,
rol. 34, pp. 251-253.
SCHMIEDEN,
VIKTOR 1903 Erfolgreiche, experimentelle Vrrlagerung von Nebennierengewebe, eiii Britrag zur Lehre von den Strumae suprareiiales
aberratae. Deutseh. Ztschr. f . chir., Bd. 70, S. 453-504.
WYMAN, L. C., AND CAROLINET i m STJDEN
1932 Studics ou suprarenal iiisufficiency. XI. The growth of transplanted cortical tissue i n the rat.
S m . J. Physiol., vol. 101, pp. 662-GG7.
ZTTEMER,R. L. 193G 9 study of adrenal cortex morphology. Am. J. Path.,
vol. 12. pp. 107-114.
Документ
Категория
Без категории
Просмотров
3
Размер файла
905 Кб
Теги
gland, adrenal, function, newborn, rats, grafts, homeoplastic
1/--страниц
Пожаловаться на содержимое документа