РОЛЬ МЕЖКЛЕТОЧНЫХ ВЗАИМОДЕЙСТВИЙ В РЕГУЛЯЦИИ ЭРИТРОПОЭЗА

participating in the transduction of regulator signals at equilibrium 
hemopoiesis conditions. 
DOI:10.12737/12263

РОЛЬ МЕЖКЛЕТОЧНЫХ ВЗАИМОДЕЙСТВИЙ В РЕГУЛЯЦИИ ЭРИТРОПОЭЗА

Ю.М.Захаров, И.Ю.Мельников

Южно-Уральский государственный медицинский университет (ректор 

И.И.Долгушин), Челябинск

zaharovum@chelsma.ru

Эритропоэз 
у 
человека 
и 
млекопитающих 
протекает 
в 

эритробластических 
островках 
(ЭО), 
представленных 
«коронами» 

эритроидных клеток, окружающих макрофаги. Регуляция эритропоэза в ЭО 
осуществляется 
 
гормональной 
(эритропоэтин 
(ЭП) 
плазмы 
крови), 

симпатическской нервной и иммунной (Т-лимфоциты) системами, аутокринным 
и 
паракринным 
механизмами, 
функционирующими 
в 
ЭО 
по 
принципу 

положительной и отрицательной обратных связей. ЭП  увеличивает: 
аффинность 
КОЕэ 
к 
макрофагам 
костного 
мозга, 
рост 
числа 
ЭО,  

пролиферации и дифференциации их эритроидных клеток;  секрецию 
макрофагами 
ЭО 
эндогенного 
ЭП 
и 
глюкозаминогликанов, 
создавая  

эритропоэтическое 
микроокружение 
в 
ЭО; 
подавляет 
апоптоз 

эритрокариоцитов в ЭО. Снижение потребности тканей организма в О2 
«включает» адаптивные  ответы клеточных  компонентов ЭО,  тормозящих 
эритропоэз: снижается чувствительность к ЭП  у макрофагов костного 
мозга, образование новых ЭО, митотической активности их эритроидных 
клеток, продукция эндогенного эритропоэтина и глюкозаминогликанов, в ЭО 
резко активируется синтез тормозящих эритропоэз цитокинов  - ФНО-альфа, 
ИЛ-6.

ROLE OF CELL-CELL INTERACTIONS IN ERYTHROPOIESIS 

REGULATION

Yu.M.Zakharov, I.Yu.Melnikov.

South-Ural state medical university (rector I.I.Dolgushin), 

Chelyabinsk

zaharovum@chelsma.ru

Key words: erythroblastic island, erythropoiesis, regulation of 

erythropoiesis. 

Erythropoiesis 
in 
human 
and 
mammals 
take 
place 
in 

erythroblastic islands (EI) formed by complexation of CFU-erythroid (or 
erythroblasts) with bone marrow macrophages [5]. Consequent doubling of 
initial CFU-erythroid cell or erythroblasts in an order 1:2:4:8:16:32 
forms an erythroid “crown” of EI. The kinetic model of CFU-erythroid 
entering 
EI 
development 
and 
erythropoiesis 
pattern 
in 
its 

erythroblastic “crown” is described by our EI classification. It 
defines the EI with erythroid cells amplification in order 1:2:4:8 as 
EI of 1 class (of development), cells amplification in order 8:16 forms 
an EI of 2 class, cells amplification in order 16:32 forms a 3 class 
EI. Erythroid “crown” of 1-2-3 classes EI to proceed proliferation and 
differentiation of erythrokaryocytes. EI of 3 class develops in 
“involution” class EI, “crown” of them represented only by maturing to 
reticulocytes normoblasts. Normally, up to 20% of involution class EI 
macrophages are capable to create a new contact with CFU-erythroid, 
thus starting a new wave of erythropoiesis in erythroid “crown”. These 
EI represents a “reconstruction” class in our classification. The sum 
of total amount of all classes EI plus an amount of “reconstruction” 
class EI per bone marrow femur in rat (or per mg of haemopoietic bone 
marrow in human) represents a total amount of CFU-erythroid undergoing 
path of differentiation in EI. The sum of amount of 1 class EI plus 
“reconstruction” class EI in bone marrow per femur represents the 
intensity of CFU-erythroid involvement in differentiation. Practical 
use of this classification and calculated indexes of our laboratory 
mentioned 
above 
along 
with 
invented 
methods 
of 
functional 

characterization of EI macrophages, permanent video registration of EI 
culture, for the first time made it possible to estimate quantitative 
parameters of formation and evolutional changes in  EI erythropoiesis, 
a role of macrophages in regulation of these processes in animals and 
in human, in state of normal steady erythropoiesis, in stimulation and 
depression, and to modulate these conditions by EI culture technique 
[1,3]. Our laboratory publications clearly show that erythropoiesis 
regulation in EI is modulated by long-range regulation influences: 
humoral (erythropoietin plasma level), nervous (symphatic), immune (Tlymphocytes) regulations, aimed on a blood oxygen supply capacity to 
meet tissue oxygen requirements of a whole body. 

In hypoxic conditions these long-range regulations activate 

short-range autocrine and paracrine mechanisms of erythropoiesis 
regulation, that works on a basis of negative or positive feedback 
paths [1]. For example, blood erythropoietin reveals ability to: 1. 
augment the CFU-erythroid affinity towards bone marrow macrophages by 
stimulating adhesive molecules expression on their membranes necessary 
for EI formation, that results in increase of EI amount in 
hematopoietic tissue; 2. initiate both synthesis and secretion of 
endogenous erythropoietin production by EI macrophages, thus providing 
a backup path for erythropoiesis proceeded and for newly formed EI in a 
model of lack of blood erythropoietin; 3. activates both synthesis and 
secretion of neutral, sulfated, “oversulfated” glucose-amino-glycans by 
EI macrophages for cell-cell regulation, that increases receptor 
appearance on erythroid cells, presenting them growth factors; 4. 
augment macrophage locomotion, their contacts with CFU-erythroid and 
new formation of EI, tansport of mature erythroid “crown” EI toward 
bone marrow sinusoids 5. stimulate lymphoid cells to contact with 1 
class and “reconstruction” EI; 6. both plasma origin and endogenous 
production erythropoietin accelerates the dynamics of erythroid cells 
amplification waves in EI “crown”, reduces their apoptosis, stimulates 
normoblasts maturation processes [1,3,4]. 

The reduced tissue oxygen uptake demands of an organism 

results in a reduction of erythropoiesis and erythrocyte production up 
to 
level 
of 
necessary 
oxygen 
tissue 
supply. 
For 
example, 

posttransfusional polycythaemia in rat leads to a well known in 
experimental hematology reduction in renal erythropoietin production 
and erythropoiesis reduction that was provoked by reduced oxygen uptake 
tissue demands. We estimated typical adaptive changes in EI cell 
components, resulted in erythropoiesis reduction. Their further 
investigations 
with 
EI 
culture 
technique 
on 
posttransfused 

polycythaemic 
rat 
model 
revealed: 
1. 
sensitivity 
reduction 
to 

additional erythropoietin in culture by bone marrow macrophages, that 
prevents new EI formation; 2. lack of EI erythroid cells ability to 
respond by mitotic activity rise to erythropoietin added to culture; 3. 
EI macrophages to reduce endogenous erythropoietin production, at the 
same time markedly increase expression, synthesis and secretion of 
erythropoiesis inhibiting cytokines –
TNF-alpha, IL-6; 4. lymphoid 

cells contact inhibition with 1 class and reconstruction  class EI; 5. 
EI macrophages reduce an erythropoietic activity microenvironment in EI 
by decreasing both synthesis and secretion of glucose-amino-glycan 
fractures total amount [2]. 

References.
1.
Zakharov 
Yu.M. 
Regulation 
of 
erythropoiesis 
in 

erythroblastic islands of bone marrow. Russian J.of Physiology. 97(9): 
980-994, 2011; 

2.
Zakharov Yu.M., Melnikov I.Yu., Shevyakov S.A., Tishevskaya 

N.V. Mechanisms of erythropoiesis suppression in posttransfused 
polycythaemia. Bulletin of Ural Med. Acad. Sci. 3(49): 100-103. 2014; 

3.
Zakharov Yu.M., Rassokhin A.G. Erythroblastic island. M., 

Meditsina: 2002. 280p. 

4.
Zakharov Yu.M., Feklicheva I.V. Influence of erythropoietin 

and T-lymphocytes on erythropoiesis in culture of erythroblastic 
islands of bone marrow in polycythaemic rat. Bulletin of Ural Med. 
Acad. Sci. 1: 81-84. 2009.

5.
Bessis M. Reinterpretation des frottis sanguins. Masson. 

Paris. 107.

DOI:10.12737/12265

ВЛИЯНИЕ СЕЛЕКТИВНОЙ БЛОКАДЫ Α2A/D-АДРЕНОРЕЦЕПТОРОВ НА 

СЕРДЕЧНО-СОСУДИСТУЮ СИСТЕМУ РАСТУЩИХ КРЫС

Т.Л. Зефиров1, Л.И. Хисамиева1, Н.И. Зиятдинова1, Л.И. Фасхутдинов1, А.Л. 

Зефиров2

1Кафедра анатомии, физиологии и охраны здоровья человека (зав. каф. 
докт. мед. наук, проф. Т.Л.Зефиров) Казанского (Приволжского) 

федерального университета; 2Кафедра нормальной физиологии (зав. каф. –

чл.-корр. РАН, проф. А.Л. Зефиров) Казанского государственного 

медицинского университета

zefirovtl@mail.ru