Typical Monocyte Research Articles

Value of peripheral blood monocyte subsets and CD64 expression in the diagnosis and prognosis of sepsis

To explore the value of monocyte subsets and CD64 expression in the diagnosis and prognosis of sepsis. A prospective case-control study was designed. 30 septic patients and 30 non-septic patients who were admitted to the intensive care unit (ICU) of the PLA Army Characteristic Medical Center from March 2021 to March 2022 were enrolled. After 1, 3, and 5 days of ICU admission, peripheral blood samples were taken from patients. Flow cytometry was used to detect the proportion of monocyte subsets and the expression level of CD64 on the surface, and the difference of expression between patients in two group was analyzed. The risk variables for sepsis were analyzed using single-factor and multi-factor Logistic regression. The diagnostic efficacy of each risk factor for sepsis was determined using the receiver operator characteristic curve (ROC curve). One day after ICU admission, the proportions of monocytes and classic monocytes in white blood cells (WBC) of septic patients were significantly lower than those of non-septic patients [proportion of monocytes to WBC: (4.13±2.03)% vs. (6.53±3.90)%, proportion of classic monocytes to WBC: 1.97 (1.43, 2.83)% vs. 3.37 (1.71, 5.98)%, both P < 0.05]. The proportion of non-classical monocytes in monocytes was significantly higher in septic patients than that in non-septic patients [(11.42±9.19)% vs. (6.57±4.23)%, P < 0.05]. The levels of CD64 expression in monocytes, classic monocytes, intermediate monocytes and non-classic monocytes were significantly higher in sepsis patients than those in non-septic patients [mean fluorescence intensity (MFI): 13.10±6.01 vs. 9.84±2.83 for monocytes, 13.58±5.98 vs. 10.03±2.84 for classic monocytes, 13.48±6.35 vs. 10.22±2.99 for intermediate monocytes, 8.21±5.52 vs. 5.79±2.67 for non-classic monocytes, all P < 0.05]. Multivariate Logistic regression research showed that CD64 in typical monocytes [odds ratio (OR) = 1.299, 95% confidence interval (95%CI) was 1.027-1.471, P = 0.025] and the proportion of non-typical monocytes in monocytes (OR = 1.348, 95%CI was 1.034-1.758, P = 0.027) were the independent risk factors for sepsis. ROC curve showed that the area under the ROC curve (AUC) of CD64 expression of classical monocytes, the fraction of non-classical monocytes in monocytes, and procalcitonin (PCT) in the diagnosis of sepsis was 0.871. A correlation analysis revealed a negative relationship between the acute physiology and chronic health status evaluation II (APACHE II) on the first, third, and fifth days following ICU admission and the expression level of CD64 in patients' classic monocytes (r values were -0.264, -0.428 and -0.368, respectively, all P < 0.05). Combining the proportion of non-classical monocytes in monocytes, the level of plasma PCT, and the CD64 expression of classic monocytes in peripheral blood has good efficacy in identifying sepsis and assessing its severity.

Issue Highlights — May 2021

Issue Highlights — May 2021

Clinical and hematologic features of experimental theileriosis in roan calves (Hippotragus equinus)

Theileria sp. (sable) infection commonly causes significant calf mortality in endangered roan antelopes (Hippotragus equinus). Schizont-induced leukocyte transformation and systemic immune dysregulation with associated cytopenias characterizes theileriosis in livestock. Data on related hematologic alterations are scarce in roan antelopes. The objective of this study was to investigate temporal changes in selected clinical parameters and hematologic measurands in experimentally infected (EI) roan calves. Six of eight calves developed theileriosis after inoculation with a Theileria sp. (sable)-infected tick stabilate. Consecutive measures of rectal temperature, lymph node size, white blood cell count (WBC), packed cell volume (PCV), hemoglobin concentration, differential leukocyte counts, leukocyte and erythrocyte morphology and percentage parasitemia were recorded. Data were compared with 15 age-matched PCR-negative control calves and nine older immune animals that had recovered from natural infection. Two non-pyrexic EI calves recovered uneventfully. Six pyrexic calves were treated, four of which died. Time to pyrexia and/or observation of schizonts and piroplasms was approximately two weeks. Total WBCs were unchanged post-infection (PI); neutrophils and typical monocytes decreased whereas typical lymphocytes (Ls) and atypical mononuclear leukocytes (AMLs), which were grouped together, increased. Parasitized and non-parasitized lymphocyte and AML (L/AML) size increased significantly PI. Piroplasms occurred intermittently at low frequencies («1 % of erythrocytes) after infection. Fatally infected calves were dehydrated, anemic, and icteric with hemorrhages and multi-organ infiltration by AMLs. The PCV and hemoglobin concentration increased PI, and platelet clumps were consistently observed. Experimental acute theileriosis in roan antelopes follows a similar pattern of disease progression to that in domestic livestock. Parasitized and non-parasitized AMLs are pivotal to the pathogenesis and require phenotypic characterization if we are to further our understanding of disease progression and severity in roan antelopes.

Novel Nanoparticulate and Ionic Titanium Antigens for Hypersensitivity Testing.

Titanium is used in a wide variety of materials ranging from medical devices to materials used in everyday life. Adverse biological reactions that could occur in patients, consumers, and workers should be monitored and prevented. There is a lack of available agents to test and predict titanium-related hypersensitivity. The aim of this study was to develop two bioavailable titanium substances in ionic and nanoparticulate form to serve as antigens for hypersensitivity testing in vitro. Peripheral blood mononuclear cells from 20 test subjects were stimulated with the antigens and secretion of monocytic and lymphatic cytokines and chemokines were measured by a multiplex bead assay. Lymphocyte stimulation indices were also determined in a subset of test subjects by measuring CD69 and HLA-DR expression by flow cytometry. Cytokine profiling revealed that both antigens increased production of typical monocyte and macrophage secreted cytokines after 24 h, with significant increases in IL-1β, IL-7, IL-10, IL-12, IL-2R, IL-6, GM-CSF, TNF-α, IL-1RA, MIP-1α, MIP-1β, IFN-α, and IL-15. Lymphatic cytokines and chemokines were not significantly induced by activation. After seven days of stimulation, ionic-Ti (2.5 μg/mL) caused proliferation (stimulation index > 2) of CD4+ cells and CD8+ cells in all persons tested (N = 6), while titanium dioxide nanoparticles (50 μg/mL) only caused significant proliferation of CD4+ cells. Our preliminary results show that the experimental titanium antigens, especially the ionic form, induce a general inflammatory response in vitro. A relevant cohort of test subjects is required to further elucidate their potential for predictive hypersensitivity testing.

Expansion of a Population of Large Monocytes (Atypical Monocytes) in Peripheral Blood of Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Diseases.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is closely associated with airway inflammation including monocytes, lymphocytes, and neutrophils. Monocytes play an essential role in the pathogenesis of chronic obstructive pulmonary disease (COPD). To elucidate the association of circulating monocyte alteration with AECOPD, we analyzed monocyte subpopulation in the peripheral blood of 16 healthy volunteers and 22 AECOPD patients at the stages of admission and remission after clinical therapy. We found a dramatic increase of a previously unreported population of large size circulating atypical monocytes (A Mo) in AECOPD patients, characterized by higher forward scatter and lower side scatter values than the typical monocytes (T Mo) which were observed predominantly in healthy individuals. Further analysis showed that A Mo expressed higher levels of CD16, intercellular adhesion molecule 1 (ICAM-1), and chemotactic protein-1 receptor-2 (CCR2) than T Mo. In contrast, the expression of class II antigen (HLA-DR) by A Mo was lower than T Mo. More importantly, we observed that the percentage of circulating A Mo among total monocytes correlated with the length of hospital stay (time to remission) and disease duration. The data suggest that circulating A Mo might have the potential to serve as a biomarker in the diagnosis and prognosis of AECOPD.

Aspectos morfológicos e ultraestruturais de células sanguíneas de Crotalus durissus terrificus

RESUMO: A avaliação hematológica, de importância comprovada como um meio auxiliar de diagnóstico ao clínico de pequenos animais domésticos, vem se tornando comum em animais selvagens não apenas para a clínica, mas para a avaliação do manejo e como estudo auxiliar para a fisiologia das várias espécies. Tendo em vista o aumento da demanda para a produção de várias drogas de importância farmacêutica, a criação de serpentes peçonhentas vem se tornando comum a ponto destes animais já serem reconhecidos como sendo de produção. O conhecimento do manejo e da clínica destes animais ainda é escasso e a mortalidade é elevada nos criatórios, tornando urgente a ampliação destes. Embora alguns estudos hematológicos já tenham sido realizados em cascavéis (Crotalus durissus) os dados analisados ainda são insipientes, notadamente em relação à caracterização das células do sangue e poucos estudos em microscopia eletrônica foram realizados em serpentes. Com o objetivo de caracterizar as células sanguíneas morfologicamente, sob microscopia óptica e ultraestrutural, foram coletadas amostras de sangue de 52 de indivíduos da subespécie Crotalus durissus terrificus para a realização de esfregaços sanguíneos e avaliação ultraestrutural. Concluiu-se que a coloração hematológica de Giemsa permite a avaliação morfológica e a diferenciação das células sanguíneas em serpentes assim como a visualização de hemoparasitos. A avaliação ultraestrutural permite evidenciar as organelas celulares e a diferenciação entre as células, inclusive entre os tipos leucocitários, porém ainda são necessários outros estudos para que seja elucidada a hipótese da existência dos eosinófilos na espécie estudada assim como é necessária melhor caracterização dos grânulos dos azurófilos para que se confirme uma possível diferença entre os monócitos típicos e os azurófilos.

Immune cells and cardiovascular health in premenopausal women of rural India chronically exposed to biomass smoke during daily household cooking

Changes in cells of the immune system are important indicators of systemic response of the body to air pollution. The aim of this study was to investigate the immunological changes in rural women who have been cooking exclusively with biomass for the past 5years or more and compare the findings with women cooking exclusively with liquefied petroleum gas (LPG). We conducted a cross-sectional analysis of the associations between indices of indoor air pollution (IAP) and a set of immune assays. Biomass users illustrated marked suppression in the total number of T-helper (CD4+) cells and B (CD19+) cells while appreciable rise was documented in the number of CD8+ T-cytotoxic cells and CD16+CD56+ natural killer (NK) cells. A consistent finding among biomass users was rise in regulatory T (Treg) cells. Among biomass users, peripheral lymphocyte subpopulations, Treg cells, and the number of typical monocytes (CD16−CD64+ cells), antigen presenting types (CD16+CD64− cells) and plasmacytoid cells (CD16−CD64− cells) were found to be significantly altered in those who daily cooked with dung in comparison to wood and crop residue users (p<0.05). Biomass users who cooked in kitchens adjacent to their living areas had significant changes in peripheral lymphocyte subpopulations, typical monocytes (CD16−CD64+) with high phagocytic activity and antigen presenting monocytes (CD16+CD64−) against women who cooked in separate kitchens (p<0.01). This study has shown that women who cooked exclusively with biomass fuel had alterations in immune defense compared with their neighbors who cooked with LPG.

Generation of Mature Murine Monocytes from Heterogeneous Bone Marrow and Description of Their Properties

Monocytes are involved in a wide range of physiological and pathological processes, many of which are studied in mouse models. Current protocols to isolate murine monocytes are few and result in unsatisfactory cell yield and purity. Here, we describe a novel approach to efficiently differentiate large numbers of mature inflammatory monocytes from heterogeneous bone marrow cell suspensions. Bone marrow cell suspensions were isolated by flushing femurs and tibias from Balb/c and C57Bl/6 mice, supplemented with macrophage colony-stimulating factor (M-CSF), and were cultured on ultra-low attachment surfaces to inhibit adherence-mediated maturation. Cells were harvested at indicated time points, underwent time-line analysis of the differentiation processes, and were subsequently extensively phenotyped to verify their monocytotic properties. In order to confirm downstream compatibility, we tested for typical monocyte behavior. Our protocol yielded 24 ± 6 × 10(6) differentiated cells per donor mouse, 10-fold higher than yields obtained using previously described peripheral blood isolation methods. Differentiated cells consisted of approximately 47% ± 12% monocytes, the rest being mature macrophages. We increased monocyte purity to 86% ± 6% by depleting adherent macrophages. Our findings indicate that bone marrow-derived monocytes (BMDMs) are an attractive tool to study, for example, the innate and adaptive immune system, atherosclerosis, and cellular migration during infection. Moreover, BMDM transplantation could be used to test novel, therapeutic in vivo approaches in mice disease models.

Dendritic cells in infectious disease, hypersensitivity, and autoimmunity

Dendritic cells are thought to direct subsequent T lymphocyte-driven adaptive immune responses (Th1/Th2) following interaction with either endogenous or exogenous antigens. These cells have an integral role in the pathogenesis of countless infectious diseases, but their role is most vividly illustrated in human immunodeficiency virus/acquired immunodeficiency syndrome and tuberculosis. Dendritic cells can arise from either myeloid or lymphoid progenitors, but the former is more common. Of particular importance are myeloid-related dendritic cells, plasmacytoid dendritic cells, infiltrating inflammatory dendritic epidermal cells, and Langerhans cells. Myeloid-related dendritic cells resemble typical monocytes, but produce cytokines that favor the cell-mediated immune response. Plasmacytoid dendritic cells resemble plasma cells, but have additional antigen-processing capabilities, and their major role is to produce interferon alpha and beta in response to viral infections. Inflammatory dendritic epidermal cells express the highest concentration of costimulatory molecules known in any cell lineage. Langerhans cells are the chief dendritic cells of the skin, and play a pivotal role in hypersensitivity and autoimmune patholo- gies, such as atopic dermatitis and psoriasis. Lastly, reduced glutathione has been implicated in modulation of the cytokine profiles of professional antigen-presenting cells, and holds promise as a future immunotherapeutic agent. This review discusses in detail the origin, characteristics, and overall functions of different types of dendritic cells. Furthermore, we have also highlighted the role of dendritic cells in infectious diseases and autoimmune diseases, with special reference to human immunodeficiency virus, tuberculosis, atopic dermatitis, and psoriasis.

Biliary pancreatitis-associated ascitic fluid activates the production of tumor necrosis factor-α in acinar cells*

Acute pancreatitis is associated with increased cytokine release from different cell sources. We have investigated the ability of acinar cells, in comparison with inflammatory peripheral blood cells, to produce tumor necrosis factor (TNF)-alpha in response to pancreatitis-associated ascitic fluid (PAAF). Controlled, randomized animal study. University research laboratory. Male Wistar rats. Flow cytometry using phycoerythrin-labeled monoclonal anti-TNF-alpha antiserum. PAAF (20%, v:v) obtained from rats with acute pancreatitis induced by bile-pancreatic duct obstruction significantly increased TNF-alpha production in acinar cells, as measured by flow cytometry using phycoerythrin-labeled monoclonal anti-TNF-alpha antiserum. Neither heating of PAAF nor the addition of soybean trypsin inhibitor or neutralizing amounts of anti-TNF-alpha monoclonal antiserum reduced the acinar cell TNF-alpha production. Monocytes and lymphocytes did not produce TNF-alpha in response to PAAF. Likewise, the typical monocyte and lymphocyte stimulating factors-lipopolysaccharide (10 microg/microL) and phorbol 12-myristate 13-acetate (250 ng/mL) plus ionomycin (1 microg/mL), respectively-were not able to produce TNF-alpha in acinar cells. By comparison of the two acinar cell populations differentiated by flow cytometry, R2 cells (with higher forward scatter values) showed a greater ability to produce TNF-alpha in response to PAAF than R1 cells. Acinar cell nuclear factor-kappaB was activated, but TNF-alpha production was not totally inhibited in presence of N-acetyl cysteine (30, 100 mM). The production of TNF-alpha from different cell sources is selectively activated. PAAF may be involved in the pathophysiology of acute pancreatitis by TNF-alpha production in acinar cells through mechanisms partially mediated by nuclear factor-kappaB activation. PAAF components, such as TNF-alpha or trypsin, are not responsible for acinar cell activation. TNF-alpha was induced by heat-resistant PAAF factors, displaying acinar cells with higher forward scatter (R2) a greater ability to increase the TNF-alpha production than R1 cells.

Selective induction of the monocyte-attracting chemokines MCP-1 and IP-10 in vesicular stomatitis virus-infected human monocytes.

It is characteristic of viral infections that monocytes/macrophages and lymphocytes infiltrate infected tissue, and neutrophils are absent. CC and non-ELR CXC chemokines predominantly attract mononuclear leukocytes, whereas the ELR motif-expressing CXC chemokines primarily act on neutrophils. To investigate the general role of chemokines in viral diseases, we determined their release and expression patterns after infection of human monocytes with vesicular stomatitis virus (VSV). Human monocytes were productively infected by VSV. Surprisingly, VSV did not induce the release of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6. In contrast, we found a strong induction of the CC chemokine monocyte chemotactic protein-1 (MCP-1) and the non-ELR CXC chemokine interferon-gamma (IFN-gamma) inducible protein-10 (IP-10) by VSV on the gene and protein level. The expression and release of the neutrophil chemoattractants IL-8 and growth-related oncogene-alpha (GRO-alpha) remained unaffected after VSV infection. Our results indicate that the typical monocyte and lymphocyte-dominated leukocyte infiltration of virus-infected tissue is based on a selective induction of mononuclear leukocyte-attracting chemokines.

Peripheral blood mononuclear phagocytes mediate dissemination of murine cytomegalovirus

Cytomegalovirus is transmitted with blood and organs from seropositive individuals, although the particular leukocyte population harboring latent or persistent virus remains poorly characterized. Murine cytomegalovirus, tagged with the Escherichia coli lacZ gene, was used to identify cells in which virus replicates during acute infection of immunocompetent mice. Recombinant murine cytomegaloviruses, RM461, RM460, and RM427, were constructed to express beta-galactosidase under control of the human cytomegalovirus ie1/ie2 promoter/enhancer. The lacZ gene was inserted between the ie2 and sgg1 genes in RM461 and RM460, disrupting a 0.85-kb late transcript that was found to be dispensable for replication in cultured cells as well as for infection of mice. In BALB/c mice, lacZ-tagged and wild-type viruses exhibited a similar 50% lethal dose and all had the capacity to latently infect the spleen. Peripheral blood mononuclear phagocytes were the major infected leukocyte cell type, as demonstrated by the ability of infected cells to adhere to glass and to phagocytize latex beads; however, these cells did not exhibit typical monocyte markers. Plaque assay for virus and 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining of frozen sections of organs from infected mice revealed that the major target organs included the spleen, adrenal glands, liver, and salivary glands, although tissues as diverse as brown fat and lungs were also involved. Individual blue-staining cells were readily identified in all infected tissues. These studies identified a mononuclear phagocyte, possibly a macrophage or dendritic cell precursor, as the vehicle of virus dissemination during acute infection, and demonstrate the utility of using lacZ-tagged murine cytomegalovirus for tropism, pathogenesis, and latency studies.

Hypertensive structural changes in blood vessels: do endothelial cells hold the key?

In recent decades, the complexity of the endothelium and its major role in maintaining or altering blood vessel architecture are being revealed. In contrast, the vascular smooth muscle cell previously received the most attention. I suggest support of the hypothesis that the endothelium is the key to vascular disease. An altered endothelium in diabetes mellitus likewise is likely to be pivotal in vascular complications that develop. We have demonstrated that adherent monocytes, indicators of altered endothelium, occur in deoxycorticosterone acetate induced hypertension in male Wistar rats. The coronary artery and thoracic aorta were investigated using transmission electron microscopy. Details of hypertensive changes were revealed as well as early atherogenic pathology in the absence of dietary modifications. Scanning electron microscopy of thoracic aorta showed details of the luminal endothelial surface and adherent monocyte-macrophages in hypertensive animals. There were two cell types: numerous typical monocytes with upstream tails, and larger cells that may have been free grazing macrophages or macrophages that had returned to the circulation. Debris and amorphous material were particularly evident in vessels from hypertensive animals. Monocytes squeezed between intact endothelial plasma membranes (as seen in section), and were found as subendothelial foam cells and phagocytosing macrophages. The endothelial adherence of monocytes to the aortas from diabetic animals was significantly (p less than 0.05) elevated over that found in controls (but not different from control-hypertensive or diabetic-hypertensive animals) supporting the concept of altered endothelium in diabetes.

Preliminary characterization of accessory cells in the nonadherent fraction of human blood mononuclear cells.

We investigated why peripheral blood mononuclear cells rigorously depleted of adherent cells by sequential incubation on plastic and nylon wool remained fully responsive to both antigenic and mitogenic signals. Nylon wool nonadherent cells (NWNA) depleted of cells expressing HLA-DR by monoclonal antibody and complement lysis did not respond to tetanus toxoid (TT) or suboptimal concentrations of phytohemagglutinin (PHA). Addition of adherent accessory cells to these NWNA HLA-DR- cells reconstituted the response to stimuli. NWNA, fractionated by discontinuous density gradient centrifugation, contained high density cells which were unresponsive alone to optimal concentrations of both TT and PHA. All the lower density fractions contained cells which were accessory for higher density cell responses to stimuli. The lowest density fraction was approximately 30% monocytes (esterase and peroxidase positive) and less than or equal to 3% B lymphocytes (surface IgG bearing). The other low density fractions contained large granular lymphocytes but rarely monocytes and no B lymphocytes. Depletion of OKT3+, OKM1+, and Leu-11+ cells from lower density cells by monoclonal antibody and complement lysis did not abolish their accessory activity, but depletion of HLA-DR+ cells or gamma irradiation of these cells decreased their accessory activity for PHA and eradicated accessory activity for TT. Thus, the responsiveness of NWNA to soluble antigenic and mitogenic signals is due, in part, to the presence of low density cells which are radiosensitive and phenotypically HLA-DR+ OKT3-OKM1-Leu-11-. Accessory activity in NWNA seems to reside, therefore, in a cell which is not a typical monocyte, natural killer cell, nor B or T lymphocyte.

Development of macrophages in the lungs of fetal rabbits, rats, and hamsters.

Fetal rabbits (days 13-32), rats (days 14-22), and hamsters (days 11-15) and selected postnatal animals were examined for pulmonary macrophages or their precursors in 2-micron sections stained by PAS-lead hematoxylin (all species), electron micrographs (rabbit and rat), and cytochemical incubations for acid phosphatase (rabbit and rat), aliesterase, and N-acetyl glucosaminidase (rabbits). All methods revealed macrophages in perinatal specimens. The appearance and distribution of these cells were compared in the different preparations to establish the reliability of PAS-lead hematoxylin for identifying them in less developed fetal lungs, where they are less active for lysosomal enzymes the earlier the stage examined. In the sections, macrophages are seen to possess a round or indented nucleus, an irregular contour, and a deep purplish-gray cytoplasm containing a variety of pink PAS-stained granules, equated with heterolysosomes by ultrastructural cytochemistry. In less developed lungs, macrophages occur along with putative precursors having a more rounded outline and fewer PAS-stained granules. In pseudoglandular lungs these precursors predominate over rather vacuolated macrophages resembling Hofbauer cells. In all three species both cell types first appear in the stroma during the bronchial bud stage and are frequently seen to divide from that time on. The earliest precursors have a relatively sparse cytoplasm which later increases in daughter cells. Hofbauer-like cells disappear during the canalicular stage of development, replaced by macrophages and transitional forms from the more rounded precursors. In day 21 rabbit lungs, scattered stromal cells are reactive for aliesterase, and, some days later, for acid phosphatase and glucosaminidase. Free mononuclear cells are rare in airways of pseudoglandular lungs but become common later. A day or two before birth in rats, free cells range between rather undifferentiated leukocytes to typical macrophages, but cells with the macrophage's complete repertory of inclusions are seen only after birth. In the fetus, typical monocytes were not identified in either the pulmonary stroma or the airways. A replicating population of macrophage-like cells therefore resides in fetal lungs. It is established before bone marrow is formed and, in rats, before monocytes have appeared in the circulation.

Identification of human mononuclear cells by anti-monocyte serum.

An antiserum to human leukaemic monocytes was raised in rabbits. Adsorption with human thymocytes and chronic lymphatic leukaemia cells rendered the antiserum specific for cells of the human myeloid and monocytic cell series. Additional adsorption with granulocytes left a weak, but specific, activity for monocytes. The cells in normal peripheral blood with which the antiserum reacts by an immunoperoxidase technique have typical monocyte morphology. Cells with typical lymphocyte morphology do not react with the antiserum, but a few cells with intermediate morphology were also stained by the antiserum. Using the antiserum as a marker, the precursor cells of the monocytic and myeloid cell series were traced in the bone marrow.

Type and course of the inflammatory cellular reaction in acute angiotensin-hypertensive vascular disease in rats.

The inflammatory cellular reaction in arterioles damaged by acute experimental angiotensin‐hypertension in rats has been examined 1, 3, 6, 12, 24 and 48 hours after the termination of the hypertensive period. The cellular reaction was predominantly composed of mononuclear cells derived from the blood. The majority of these cells, which were able to phagocytize, looked like lymphocytes, and the rest like typical monocytes. The cellular reaction began as a sticking phenomenon corresponding to the damaged endothelium followed by a penetration of mononuclear cells into the arteriolar walls. The cells left the walls of the arterioles after having carried out the macrophage function, returning directly to the circulation or penetrating through the arteriolar wall to the connective tissue surrounding the arteriole. A marked periarteriolar cellular infiltration like that seen in cases of chronic hypertensive vascular disease in different experimental animals was produced by prolonging the number of days (from one to four) in which experimental angiotensin‐hypertension was induced. Rats treated with cortisone showed absence of or decreased inflammatory cellular reaction and a 2–3 times slower elimination of fluorescent proteins deposited in the arterioles as compared with that found in controls. The delayed elimination is thought to be caused by the decrease in or lack of cellular reaction.