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PubMedDate not supplied

[Histo-architectonic features of the autonomic nerve terminals and their cellular microenvironment in breast cancer tissues before and after radiotherapy].

The difference in the histoarchitectonics of structures of vegetative nervous terminals (VNT) before and after radiotherapy (RT) indicates the existence of VNT fragments sensitive and resistant to radiation damage. Heterogeneity of the local neuromediator background in tumor morphogenesis before and after RT can be clarified through studying the VNT cellular microenvironment.

Adolescent↗
PubMed2004

Efficient gene transfer into primitive hematopoietic progenitors using a bone marrow microenvironment cell line engineered to produce retroviral vectors.

BACKGROUND AND OBJECTIVES: Effective gene transfer into human hematopoietic stem/progenitor cells is a compromise between achieving high transduction efficiency and maintaining the desired biological characteristics of the target cell. The aim of our work was to exploit the stromal microenvironment to increase gene transfer and maintenance of hematopoietic progenitors. DESIGN AND METHODS: The murine bone marrow stromal cell line MS-5, known to support primitive human progenitors, was modified into an amphotropic packaging cell, by the stable introduction of DNA coding for retroviral structural proteins, and a viral vector encoding a marker gene. The gene transfer efficiency of the recombinant virus was evaluated by flow cytometry, in vitro assays for committed (CFC) and primitive (LTC-CFC) progenitors, as well as a clonal assay for B and NK lymphoid progenitors. RESULTS: The new packaging cell line (NEXUS) produced equivalent levels of virus as did the established GP+Am12 system, also under serum-free conditions. On average 30% of human mobilized peripheral blood CD34(+) cells were transduced by a single exposure to NEXUS supernatant, representing a three-fold increase over GP+Am12-based technology. Gene transfer into both committed and primitive progenitors increased on average two-fold using NEXUS retroviral supernatant. Furthermore, CD34(+) CD38(low) early progenitor cells purified from umbilical cord blood were efficiently transduced with NEXUS retroviral vector and gave rise to a high frequency of marked B and NK lymphocytes. INTERPRETATION AND CONCLUSIONS: Our data show that that an established bone marrow stromal cell can be engineered to enhance the genetic modification of primitive hematopoietic and lymphoid progenitors using a clinically relevant method.

Animals↗
PubMedDate not supplied

[Role of hematopoietic microenvironment in the mechanism of radioprotective action of interleukin-1 beta in long-term bone marrow cultures].

The influence of human interleukin-1 beta in different concentration on processes of postirradiation recovery of haemopoietic precursors (GM-CFC) and morphology of recognized elements of bone marrow were studied in long-term bone marrow cultures during 28 days after gamma-irradiation with a dose of 2 Gy. It was studied also the action of interleukin-1 beta on proliferation, the contents of GM-CFC and the induction of GM-CSF in non-irradiated cultures. It was shown that the injection of interleukin-1 beta increased proliferation and the content of GM-CFC and also raised an induction of GM-CSF in the non-irradiation cultures. The maximum increase of a level of GM-CSF, amount of GM-CFC and proliferation of GM-CFC was marked in 20 hours after the injection of cytokine. Under irradiation of long-term bone marrow cultures the maximum stimulation effect to recovery of GM-CFC, total number of myelocaryocytes and the content of immature and mature granulocytes were observed after the injection of interleukin-1 beta in concentration of 0.005 microgram/ml 20 hours prior to radiation exposure. The data of this report suggest that one of the mechanisms of radioprotective action of interleukin-1 beta apparently is connected with stimulation action on hematopoietic microenvironment cellular elements that causes the release of GM-CSF or/and other cytokines, and stimulation recovery of haemopoietic precursors.

Animals↗
PubMed2002

The intracellular microenvironment in host cell-specific phosphorylation of SNT1 by the FGFR1 tyrosine kinase.

The phosphorylation of the fibroblast growth factor receptor (FGFR) kinase substrate SNT1 (also called FGFR substrate 2, FRS2) by FGFR tyrosine kinases is both host cell- and receptor isotype-specific. To study the determinants of the host cell-specific phosphorylation of SNT1 by FGFR1 tyrosine kinase, we constructed a chimeric receptor FGFR2IIIb/R1 that consisted of an FGFR2IIIb ligand-binding ectodomain and an FGFR1 tyrosine kinase domain. The chimeric FGFR2IIIb/R1 kinase mediated robust phosphorylation of SNT1 immediately after transfection in mouse 3T3 cells where the FGFR1 kinase was residential, and in proliferative aged prostate tumor epithelial cells (DTE-R1/100) that ectopically expressed FGFR1 kinase. This is in contrast to the fact that the robust phosphorylation of SNT1 by ectopic FGFR1 kinase is an acquisition property in DTE premalignant prostate epithelial cells, which normally do not express FGFR1. The data suggest that the microenvironment of intracellular, rather than components in the extracellular compartment, of host cells is important in permitting FGFR1 kinase to strongly phosphorylate SNT1. Together with our previous data that the acquisition of SNT1 phosphorylation activity is concurrent with the acquisition of mitogenic activity of FGFR1 in prostate epithelial cells, the results here further demonstrate that the phosphorylation of SNT1 is host cell specific and that alterations induced by chronic exposure to ectopic FGFR1 kinase are involved in acquisition of SNT1 phosphorylation activity to the ectopic FGFR1 in prostate epithelial cells.

3T3 Cells↗
PubMed2004

Bone marrow microenvironment facilitating dendritic cell: CD4 T cell interactions and maintenance of CD4 memory.

This study shows that bone marrow (BM) stroma expresses constitutively multiple adhesion molecules (ICAM-1, VCAM-1, MadCAM-1, P-selectin) relevant for the homing and infiltration of BM by blood derived T lymphocytes, and also the co-stimulatory molecule CD80, relevant for T cell activation. T cells were capable of homing to BM but not to thymus. Homing to BM involved the integrins LFA-1alpha and alpha4 which interact with the above constitutively expressed cell adhesion molecules (CAMs). CD3 T cells were detected together with BM resident CD11c dendritic cells (DCs), often enriched in follicle-like structures in BM parenchyma. Cognate interactions between transferred antigen specific transgenic CD4 T cells and antigen laden BM-DCs led to formation of multicellular clusters in situ in BM, to generation of lymphoblasts and to clonal T cell expansion within such clusters. The great majority of BM-CD4 T cells had a memory phenotype suggesting that the BM microenvironment facilitates maintenance of CD4 memory. These results extend and corroborate our previous findings on BM-CD8 T cell mediated immune responses. Together these findings suggest that DC-T cell interactions in BM play an important role in immune responses to blood-borne antigen and in the establishment of systemic immunity and long-term memory.

Animals↗
PubMed2004

The RANK/RANK ligand system is involved in interleukin-6 and interleukin-11 up-regulation by human myeloma cells in the bone marrow microenvironment.

BACKGROUND AND OBJECTIVES: The receptor activator of NF-kB ligand (RANKL) has a critical role in osteoclast activation. Recently it has been demonstrated that human multiple myeloma (MM) cells do not express RANKL but up-regulate RANKL in bone marrow stromal cells (BMSC). To further investigate the role of RANKL in the pathophysiology of MM we evaluated the expression of its receptor RANK in MM cells and in the BM environment and the potential role of RANKL in the interaction of myeloma cells with the microenvironment. DESIGN AND METHODS: RANK mRNA and protein expression were evaluated by reverse transcription polymerase chain reaction and Western blot analysis in human myeloma cell lines (HMCL), fresh purified MM cells, BMSC and endothelial cells. Moreover the effect and the role of RANKL on cytokine secretion were evaluated in BMSC, in endothelial cells and in co-culture conditions with myeloma cells. RESULTS: We found that RANK is expressed in BMSC and endothelial cells but not in myeloma cells. Consistently, RANKL did not have a direct effect on myeloma cell survival, but RANKL treatment induced a significant increase of interleukin (IL)-6 and IL-11 secretion by both BMSC and endothelial cells. Moreover, in a co-culture system we found that myeloma cells up-regulated both IL-6 and IL-11 secretion by BMSC and endothelial cells through cell-to-cell contact. The presence of the RANK-Fc that blocks the RANK/RANKL interaction significantly inhibited HMCL-induced secretion of IL-6 and IL-11. INTERPRETATION AND CONCLUSIONS: Our data provide new notions on the role of the RANKL system in the pathophysiology of MM.

Bone Marrow↗
PubMedDate not supplied

[The role of hematopoietic microenvironment in prodigiozan' mechanism of action on postradiation recovery of hemopoiesis in long-term bone marrow cultures].

Influence of prodigiozan in different concentrations on the process of postirradiation recovery of haemopoietic precursors (GM-CFC) and morphologically recognizable elements of the bone marrow were studied in long-term bone marrow cultures during 28 days after 2 Gy gamma-irradiation. Also, prodigiozan was studied for action on the contents of GM-CFC and induction of GM-CSF three, 24 and 48 hours after injection in cultures unexposed to radiation. It is shown that injection of prodigiozan in concentration 0.1-1.0 microg/ml 24 hours prior to irradiation stimulates postradiation recovery of GM-CFC number and a total number of myelocaryocytes in irradiation of long-term bone marrow cultures. In saved cultures there was an increase in the number of stromal cells 1 and 2 days after radiation. In non-exposed to radiation long-term bone marrow cultures injection of prodigiozan increased induction of GM-CSF and raised contents of GM-CFC. The maximal increase occurred 24 hours after introduction of radioprotector. It is suggested that one of the mechanisms of a radioprotective action of prodigiozan may be stimulation of hematopoietic microenvironment cellular elements leading to a marked release of GM-CSF or/and other cytokines and stimulation of recovery of hemopoietic precursors.

Animals↗
PubMed2004

EphA2 induction of fibronectin creates a permissive microenvironment for malignant cells.

Normal and metastatic cells continuously exchange information with the surrounding tissue environment, and this communication governs many aspects of cell behavior. In particular, the physical placement or adhesions of cells within their environment are increasingly understood to facilitate this communication. Classically, cell-cell and cell-extracellular matrix adhesions have been viewed as separable events that are independently controlled. This simple view is changing, as evidence emerges of coordinated regulation of cellular adhesions. Here, we show that the EphA2 tyrosine kinase, which is overexpressed in many aggressive cancers, regulates a fine balance of cell-cell and cell-extracellular matrix adhesions in epithelial cells. EphA2 selectively inhibits cell-cell adhesions by increasing cell attachment and up-regulating the extracellular matrix protein fibronectin. We also show that fibronectin can contribute to important aspects of malignant character. Antibody-based targeting of EphA2 inhibits malignant cell growth by decreasing fibronectin and thereby inducing apoptotic death. Our findings strengthen a concept that cancer progression is regulated by a bidirectional communication between tumor cells and their surrounding microenvironment.

Antibodies↗
PubMed2004

[Characterization of intervertebral disc--disc cells and pericellular microenvironment].

The intervertebral disc is classified as fibrocartilage, and has distinct functional and mechanical properties. The disc, composed of the nucleus pulposus and annulus fibrosus, varies in density, anatomic features, and in the morphology of their constituent cells. This heterogeneity has hampered detailed investigations of disc cellular metabolism. Focusing on the heterogeneity, we cultured disc cells under various conditions to examine the cellular metabolism, specifically glycosaminoglycan accumulation and pericellular microenvironment, and succeeded in mechanically isolating disc chondrons from annulus fibrosus. We believe that disc chondron also plays an important role in maintaining cartilageous phenotype in terms of cell-matrix interaction of the intervertebral disc.

Cell Culture Techniques↗
PubMed1992

Incidence and distribution of experimental metastases in mutant mice with defective organ microenvironments (genotypes Sl/Sld and W/Wv).

Mice carrying mutations at the Sl (steel) and W (dominant white spotting) loci develop abnormalities on 3 migratory embryonic stem cell populations: hematopoietic stem cells, neural crest-derived melanocytes, and primordial germ cells. Transplantation experiments have indicated that the Sl locus affects the microenvironment where stem cells migrate, proliferate, and differentiate, while the W locus affects the migratory cells themselves. The Sl locus encodes for a multipotent growth factor known as stem cell factor. The W locus encodes the c-kit protein tyrosine kinase receptor whose ligand is the stem cell factor. We have investigated the incidence and organ distribution of experimental metastases after systemic intra-arterial injection of B16-G3.26 melanoma cells into mutant Sl/Sld and W/Wv mice. Both mutant mouse strains had a markedly lower incidence of ovarian metastases when compared with their congenic +/+ mice. In contrast to the rare colonization of the ovaries, Sl/Sld and W/Wv mice developed metastases in the myocardium, kidney, and stomach--anatomic sites that were infrequently or never affected in their congenic nonmutant mice. The only organs in which the average number of metastatic colonies differed between Sl/Sld and W/Wv mice were the bone marrow and kidneys. The average number of colonized bones per mouse in the Sl/Sld group was 5.0 +/- 3.1 (SD), compared with 12.7 +/- 5.3 in the W/Wv group. The average number of metastatic nodules in the kidneys of Sl/Sld mice was 24.6 +/- 9, while W/Wv mice had 15.5 +/- 2.5. Mutant mice with multiple metastatic nodules in the kidneys, heart, and stomach were also found to have forestomach papillomas, an enlarged duodenum, kidney abnormalities, and small body size. The results of this study provide useful information on potential mechanisms of interaction of metastatic cells with their target organs, and suggest that there are additional organ defects associated with the mutations in the Sl and W loci. They also document the importance of mutant mice in metastasis research.

Animals↗
PubMed2005

Effect of tumor host microenvironment on photodynamic therapy in a rat prostate tumor model.

PURPOSE: Tumor host microenvironment plays an important role in tumor growth, metastasis, and response to cancer therapy. In this study, the influence of tumor host environment on tumor pathophysiology, photosensitizer distribution, and photodynamic therapy (PDT) treatment effect was examined in the metastatic at lymph node and lung (MatLyLu) rat prostate tumor. EXPERIMENTAL DESIGN: MatLyLu tumors implanted in different host environment [i.e., orthotopically (in the prostate) or s.c.] were compared for difference in vessel density, average vessel size, vascular permeability, tumor vascular endothelial growth factor production, and tumor oxygenation. Uptake of photosensitizer verteporfin in tumors in both sites was determined by fluorescence microscopy. To compare tumor response to PDT, both orthotopic and s.c. MatLyLu tumors were given the same doses of verteporfin and laser light treatment, and PDT-induced tumor necrotic area was measured histologically. RESULTS: Orthotopic MatLyLu tumors were found to grow faster, have higher vessel density and more permeable vasculature, have higher vascular endothelial growth factor protein levels, and have lower tumor hypoxic fraction than the s.c. tumors. Uptake of photosensitizer verteporfin in the orthotopic tumor was higher than in the s.c. tumors at 15 minutes after injection (1 mg/kg, i.v.), and became similar at 3 hours after injection. For the vascular targeting PDT treatment (0.25 mg/kg verteporfin, 50 J/cm(2) at 50 mW/cm(2), 15 minutes drug-light interval), there was no significant difference in PDT-induced tumor necrotic area between the orthotopic and s.c. tumors, with 85% to 90% necrosis in both types of tumors. However, tumor necrosis induced by the cellular targeting PDT (1 mg/kg verteporfin, 50 J/cm(2) at 50 mW/cm(2), 3 hours drug-light interval) was significantly different in the orthotopic (64%) versus the s.c. (29%) tumors. CONCLUSIONS: Tumor host environment can significantly affect photosensitizer verteporfin distribution and PDT treatment effect. Verteporfin-PDT regimen targeting tumor cells is more sensitive to such influence than the vascular targeting PDT. Our study showed the importance of tumor host environment in determining tumor physiologic properties and tumor response to PDT. To obtain clinically relevant information, orthotopic tumor model should be used in the experimental studies.

Animals↗
PubMed2005

Thalidomide radiosensitizes tumors through early changes in the tumor microenvironment.

PURPOSE: The aim of this work was to study changes in the tumor microenvironment early after an antiangiogenic treatment using thalidomide (a promising angiogenesis inhibitor in a variety of cancers), with special focus on a possible "normalization" of the tumor vasculature that could be exploited to improve radiotherapy. EXPERIMENTAL DESIGN: Tumor oxygenation, perfusion, permeability, interstitial fluid pressure (IFP), and radiation sensitivity were studied in an FSAII tumor model. Mice were treated by daily i.p. injection of thalidomide at a dose of 200 mg/kg. Measurements of the partial pressure of oxygen (pO(2)) were carried out using electron paramagnetic resonance oximetry. Three complementary techniques were used to assess the blood flow inside the tumor: dynamic contrast-enhanced magnetic resonance imaging, Patent Blue staining, and laser Doppler imaging. IFP was measured by a "wick-in-needle" technique. RESULTS: Our results show that thalidomide induces tumor reoxygenation within 2 days. This reoxygenation is correlated with a reduction in IFP and an increase in perfusion. These changes can be attributed to extensive vascular remodeling that we observed using CD31 labeling. CONCLUSIONS: In summary, the microenvironmental changes induced by thalidomide were sufficient to radiosensitize tumors. The fact that thalidomide radiosensitization was not observed in vitro, and that in vivo radiosensitization occurred in a narrow time window, lead us to believe that initial vascular normalization by thalidomide accounts for tumor radiosensitization.

Angiogenesis Inhibitors↗
PubMed2005

Carbonic anhydrase IX (CA IX) mediates tumor cell interactions with microenvironment.

Expression of CA IX is normally restricted to the mucosa of alimentary tract, but on the other hand, it takes place in a high percentage of human cancers derived from tissues which are normally CA IX-negative. It is a transmembrane protein with two extracellular domains: carbonic anhydrase (CA) with a high catalytic activity and a proteoglycan-like segment (PG), mediating cell-cell adhesion. Both CA and PG domains interact with the microenvironment and they could play a role in tumorigenesis, but their roles are poorly understood. The present work characterizes some newly recognized properties of the PG. One of them is a prevalently negative charge, caused by a high proportion of dicarboxylic amino acids. This is reflected by easy dissociation of complexes formed by PG either with monoclonal antibody M75 or with the cell surface receptor already at slightly acidic pH. This property might facilitate separation of cells from the primary tumor. Released cells may subsequently attach elsewhere in the organism and eventually start metastatic growth. Another aim of the present study was to identify human tumor cell lines which are expressing the presumed CA IX receptor molecule. The same cell lines were also tested for the presence of CA IX protein; we found that expression of CA IX and of the receptor is independent of each other. In addition, we examined the species specificity of CA IX receptors. The PG domain, which contains the epitope of mAb M75 -PGEEDLP- overlapping with the binding site for putative receptor is relatively conserved in evolution: human and rat CA IX cross-react with M75 antibody on western blots. Consistently with this, human and rat cells can attach to purified human CA IX protein. On the other hand, murine CA IX contains an entirely different equivalent of PG sequence and it does not react with M75 antibody or attach to human CA IX protein. This is suggestive of the co-evolution of CA IX protein together with its receptor.

3T3 Cells↗
PubMed2001

[Tumor escaping mechanisms present in microenvironment of laryngeal cancer].

In tumor tissue obtained from a group of 21 patients treated surgically for laryngeal carcinoma, the expression of Fas, Fas-L, CD3, TCR zeta chain and Bcl-2 were estimated. It has been shown that tumor often express: Fas-L, Fas, Bcl-2, the molecules which may influence increased tumor survival. On the other hand lack of MHC class I antigen expression on tumor cells frequently has been observed. As it is known, such tumor cells can not be recognized by cytotoxic T lymphocytes. Frequently observed decreased expression of TCR zeta chain and high level of apoptosis among T cells present in tumor microenvironment seems to depend on direct interactions with molecules expressed by tumor. Understanding of these interactions may be of great importance in evaluation of tumor aggressiveness, patients follow up and the approach to treatment.

Adult↗
PubMed2005

Role of the hypoxic bone marrow microenvironment in 5T2MM murine myeloma tumor progression.

BACKGROUND AND OBJECTIVES: Unlike most other tumors, multiple myeloma (MM) cells have to survive and to grow in a bone marrow (BM) microenvironment which is already hypoxic by nature. BM hypoxia is crucial for normal hematopoiesis. However, how BM hypoxia and MM affect each other is unknown. We addressed this topic in the 5T2MM mouse model. DESIGN AND METHODS: Levels of hypoxia in the BM of control and tumor-bearing mice were analyzed by flow cytometric analysis of pimonidazole hypoxyprobe binding and hypoxia-inducible factor 1alpha (HIF-1alpha) expression. Micro-vessel density was measured by CD31 staining of BM sections for immunohistochemistry. Apoptosis sensitivity of CD45 5T2MM subsets in hypoxic conditions were analyzed by detection of active caspase-3. RESULTS: Analysis of control and 5T2MM diseased mice injected with pimonidazole hypoxyprobe indicated that both normal BM and myeloma-infiltrated BM are hypoxic. However, the hypoxia in the myelomatous BM was significantly decreased. Analysis of HIF-1alpha expression, a surrogate marker of hypoxia, also demonstrated significantly lower levels of hypoxia in myeloma-infiltrated BM. HIF-1alpha expression was inversely correlated with the micro-vessel density. In vitro culture of 5T2MM cells under hypoxic conditions indicated induction of apoptosis in the CD45- MM-fraction, but not in the CD45+ 5T2MM-cells. INTERPRETATION AND CONCLUSIONS: These data suggest that native BM hypoxia is advantageous for the tumor-initiating CD45+ 5T2MM-cells. Together with the decreased hypoxia in myeloma-infiltrated BM it also indicates that myeloma-associated angiogenesis is functional and permissive for the expansion of CD45- 5T2MM-cells. All together the data raise the possibility of an important role of BM hypoxia in myeloma tumor progression.

Animals↗
PubMed2001

[Study on the correlation of the cytokine secreted by the endometrium focus and the microenvironment of the fleument fluid].

OBJECTIVE: To investigate the correlation of endometriotic focus and peritoneal fluid as well as its effect on reproduction. METHODS: Forty-three women with surgical treatment or laproscope with infertility are divided into endometriosis group (24 cases) and normal pelvic group (control group 19 cases) . The pathophysiology of patient' s peritoneal fluid, celiac macrophages and endometriotic cells are analyzed by chemotactic test on monocytes, dot blot hybridize, enzyme linked immunoadsorbent assay and the level of cytoplasmic [Ca2+]i respectively. Meanwhile, the influence of peritoneal fluid and endometriotic cells to sperm motivity as well as the effects to rat embryo cleavage are evaluated. RESULTS: The monocyte moving distance induced by peritoneal fluid in endometriosis group vs. control is (87.2 +/- 9.4) m vs. (51.9 +/- 3.7) microm (P < 0.01). The count of celiac macrophages (1.47 +/- 0.87) x 10(6)/ml vs. (0.67 +/- 0.73) x 10(6)/ml (P < 0.01), The basic expression level of monocyte chamotactic protein-1 (MCP-1) in endometriotic cells is (18.34 +/- 3.95) A. After exposured to IL-1beta and tumor necrosis factor-alpha, the OD of MCP-lmRNA is 56.84 +/- 3.21 A and 41.58 +/- 2.48 A respectively (P < 0.01 ). CONCLUSION: With the influence between endometriotic focus and microenvironment of peritoneal fluid, the level of cytokines expressed by celiac macrophages and endometriotic focus are enhanced, and it can interfere some process in reproduction.

Animals↗
PubMed2004

The morphological analysis of the haematopoietic microenvironment of the bone marrow at foetuses from preterm pregnancies.

The aim of the study was morphological assessment of the haematopoietic microenvironment of the bone marrow in foetuses from preterm pregnancies. For the morphological assessment the bone marrow was taken from sternum during an autopsy examination. After standard preparation, cellular elements of individual developmental lines were identified with the application of immunohistochemical methods. Evaluation of the bone marrow stroma elements was performed on the basis of configuration of the vascular sinuses, connective tissue elements, mutual topographic relations and integrin occurrence. The assessment of the argentophilic fibres was carried out with impregnation with silver according to the Gomori method. The configuration of the vascular sinuses was defined with morphometric evaluation with MicroImage-Olympus Kit. Identification of the 'young vascular forms' was performed with immunohistochemical methods with the use of endothelial cell antibodies and factor VIII. The presence of integrin was discovered in individual megakaryocytes, endothelial cells of sinus vessels and singular cells forming a stroma. However, no differences were found in the quantity of argentophilic fibres. The study revealed that ontogenetic development of haematopoietic tissue not only consists in alterations connected with the maturing process and cellular differentiation, but in topographic changes as well.

Bone Marrow↗
PubMed1992

[Compensation-adaptation reactions of hemopoiesis-inducing microenvironment of bone marrow in stress].

The time course of compensation-adaptation reactions of bone marrow hemopoiesis-inducing microenvironment (HIM) was studied in F1 (CBA x C57BL/6) mice subjected to 10-hour immobilization. The number of macrophage and fibroblastoid colony-forming units, committed and stem precursor stroma cells responsible for HIM transport was shown to increase in the hemopoietic tissue during adaptation syndrome. HIM activation in stress was found to be macrophage- and lymphocyte-dependent process.

Adaptation, Physiological↗