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PubMed1991

Immunohistochemical detection of high endothelial venules in extranodal B-cell lymphomas.

The hypothesis that extranodal malignant lymphomas, such as thyroid, stomach, rectum, ileum and uterus, eventuate from long-standing inflammation is essentially tested using a monoclonal antibody (HECA-452) to an endothelial-associated antigen selectively expressed by the high endothelim of post-capillary venules (HEVs) normally present in lymph nodes, tonsils and mucosa-associated lymphoid tissues. The presence of HEVs was examined on freshly prepared specimens from 16 cases of extranodal lymphoma of the B-cell type (eight thyroid, three stomach, two rectum, one ileum, one uterus, one tonsil). Control cases included reactive lymph nodes, nodal lymphoma of T-cell type, epithelial neoplasia, bone and soft tissue sarcomas, glioblastoma, thyroid affected by chronic lymphocytic thyroiditis (CLTH), thyrotoxicosis (Grave's disease) or nodular goiter, and salivary gland affected by Sjogren's syndrome (SS). HECA+ HEVs were present in reactive lymph nodes, nodal lymphoma, and all but one case of thyroid, all cases of stomach and all cases of rectal lymphoma, together with all CLTH and SS, both known to be autoimmune diseases. No thyroid, ileal or uterine lymphoma cases had any HECA positive venules. HECA+ venules were present in extranodal lymphomas, either adjoining the lymphoid follicles observed in several cases or in the diffusely proliferating tumor cells. Previous studies have shown that HEVs appeared in association with long-standing inflammation. The present study therefore, suggested that extranodal lymphomas of the thyroid, stomach and rectum evolve in long-standing inflammation, forming HEVs.

Antibodies, Monoclonal↗
PubMed1996

Further observation of leucocyte migration through the endothelium of venules in the posterior latissimus dorsi muscle of the quail-chick spinal cord chimeras.

The migration of leucocytes through the walls of venules was examined in detail in the posterior latissimus dorsi muscle of quail-chick spinal cord chimeras, in which flaccid paralysis of the wings was observed. Examinations were made from the 70th to 80th day after hatching. Muscle fibers were degenerated and intramuscular nerve bundles destroyed. Massive leucocytes (almost lymphocytes) were found around the venules, depending on the passage of wandering leucocytes through the endothelium. Lymphocytes penetrated and were encased in the cytoplasm of the venular endothelial cell, and did not pass through the interendothelial junction. These findings suggest that, in the venules of the atrophied chimeric muscle, wandering leucocytes in the blood may pass through the endothelial cell body and migrate into the inflamed extravascular space.

Animals↗
PubMed2000

Inhaled nitric oxide modulates leukocyte kinetics in the mesenteric venules of endotoxemic rats.

OBJECTIVE: to determine whether inhaled nitric oxide (NO) would alter leukocyte kinetics in the septic microvasculature. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Sprague Dawley rats. INTERVENTIONS: Rats were treated with either saline or endotoxin (10 mg/kg, iv) and then allowed to breathe either air or air plus NO (10 ppm). MEASUREMENTS AND MAIN RESULTS: After a 4-hr period, rolling, firm adhesion, and emigration of leukocytes and endothelial dysfunction were monitored in mesenteric venules by using intravital videomicroscopy. Compared with controls, endotoxemic rats exhibited a profound influx in mesenteric venule rolling leukocytes (55+/-17 vs. 70+/-19 leukocytes/min; p < .05), associated with a reduction of leukocyte rolling velocity (83+/-14 vs. 34+/-3 microm/sec; p < .05). In endotoxemic rats, venular endothelium leukocyte firm adhesion (1.15+/-0.32 vs. 4.08+/-0.96 leukocytes/ 100 microm; p < .05) and emigration (0.84+/-0.47 vs. 4.23+/-1.2 leukocytes/100 microm; p < .05) increased compared with controls. Inhaled NO had no effect on leukocyte kinetics in control rats. Inhaled NO significantly attenuated endotoxin-induced venular endothelium leukocyte adhesion (4.08+/-0.96 vs. 1.86+/-0.76 leukocytes/100 microm; p < .05) and emigration (4.23+/-1.2 vs. 1.68+/-0.72 leukocytes/100 microm; p < .05). Compared with control rats, macromolecular (FITC-dextran) vascular leakage, expressed as the perivenular/intravenular fluorescence intensity ratio, increased in endotoxemic rats (0.56+/-0.02 vs. 0.81+/-0.05; p < .01). Endotoxin-induced macromolecular vascular leakage increases were partially prevented by inhaled NO (0.66+/-0.01 vs. 0.56+/-0.02; p < .05). CONCLUSION: These observations suggest that inhaled NO reduces leukocyte adhesion and the degree of vascular permeability dysfunction in mesenteric venule of endotoxemic rats.

Administration, Inhalation↗
PubMed1995

Delayed "spontaneous" adhesion of leukocytes to rat mesenteric venules is dependent upon reactive oxidants.

We investigated the role of reactive oxygen metabolites (ROMs) as potential mediators of delayed "spontaneous" leukocyte adhesion to rat mesenteric venules after the manipulation for in vivo microscopy. Rats were anesthetized via tail vein and prepared for intravital microscopic viewing of a segment of mesenteric venule. Leukocyte rolling, adhesion, and emigration were quantitated every 30 min for 3 h. Intravital observation immediately after routine gentle manipulation revealed a substantial leukocyte rolling and a small number of adherent and emigrated leukocytes. This rolling leukocyte flux then declined to a minimal level for 60 min. The number of adherent and emigrated leukocytes did not change during the initial 90 min. After 120 min, the flux of rolling leukocytes, and adherent and emigrated leukocyte number began to increase and reached significant levels at 180 min. To determine the possible role of ROMs in this "spontaneous" adhesion, rats were treated continuously with superoxide dismutase (SOD) plus catalase given intravenously over 3 h. Rolling leukocyte flux after 120 min was significantly attenuated by SOD plus catalase. SOD + catalase also significantly inhibited delayed leukocyte adhesion and emigration. Allopurinol substantially inhibited xanthine oxidase activity but had no significant effects on the above parameters of neutrophil dynamics. These findings suggest that ROMs, probably derived from a source other than xanthine oxidase, constitute important mediators of "spontaneous" leukocyte adhesion in rat mesenteric venules.

Allopurinol↗
PubMed1997

Ischemia/reperfusion-induced leukocyte-endothelial interactions in postcapillary venules.

The recruitment of leukocytes into postcapillary venules following reperfusion of ischemic tissues is a classical inflammatory response that is influenced by a balance of adhesive and hemodynamic forces. Initial periods of reperfusion are characterized by an elevation in low affinity adhesive interactions between leukocytes and endothelial cells, which permit the leukocytes to establish intimate contact with the vascular endothelial lining as they roll across it. This rolling behavior of leukocytes increases the probability that stronger adhesive interactions between leukocyte and endothelial cell will occur, allowing the leukocyte to firmly adhere to the endothelium and subsequently to emigrate across the venular wall into the interstitial compartment. Several factors appear to contribute to the leukocyte-endothelial cell adhesion that is elicited by ischemia/reperfusion, including: 1) the magnitude of adhesion molecule expression on leukocyte and/or endothelial cell surfaces, 2) reactive oxygen metabolites and lipid mediators released from stimulated leukocytes and endothelial cells and 3) hemodynamic dispersal forces that act to sweep leukocytes from the microvessel wall. Intravital microscopic techniques have allowed investigators to focus on inflammatory responses in postcapillary venules, which is the primary site of leukocyte adhesion and vascular protein leakage. This technology has also been employed to delineate the role of adhesive and hemodynamic factors in promoting leukocyte rolling, adhesion, and emigration in postcapillary venules exposed to ischemia/reperfusion.

Animals↗
PubMed1993

Mesoglycan treatment restores defective fibrinolytic potential in cutaneous necrotizing venulitis.

BACKGROUND: Cutaneous necrotizing venulitis (CNV) is a clinical disorder associated with segmental inflammation and fibrinoid necrosis of the dermal venules. It usually presents clinically as palpable purpura, even sometimes as nodules, bullae, ulcers, and urticarial lesions. This form, when showing as leukocytoclastic vasculitis is apparently characterized by the tissue deposition of circulating immune complexes and by reduced cutaneous (CFA) and plasma (PFA) fibrinolytic activity due to reduced release of plasminogen activator (PA) from the venular endotheliocytes. Reduced CFA and PFA cause large amounts of fibrin deposits in both intra- and perivascular areas, which are able to magnify and self perpetuate the inflammatory processes following immune complex deposition. METHODS: We have studied both the PFA and CFA potential (the maximum amount of PA released in the skin after certain stimuli) and the deposits of immunoglobulins, C3, and fibrin related antigen, before and after intradermal injection of histamine (a substance able to provoke endothelial release of PA), in three subjects affected by CNV before and 20 days after 10 mg/kg/day I.M. treatment with the fibrinolytic agent mesoglycan. RESULTS: Cutaneous fibrinolytic activity and CFA potential, reduced prior to treatment, was normal after treatment, while the deposits of immunoglobulins (IgA, IgG and IgM), C3, and fibrin related antigen, detected with direct immune fluorescence (DIF) showed similar findings before and after treatment. CONCLUSIONS: These data suggest that reduced CFA may play a major role in the pathogenesis of the immunologically mediated injury in CNV. The intraperivascular deposition of fibrin is favored. The fibrinolytic agent mesoglycan seems effective in restoring defective fibrinolysis in patients affected by cutaneous necrotizing venulitis, suggesting that in cases with reduced cutaneous fibrinolytic activity (or potential) the use of a fibrinolytic agent should be considered.

Adult↗
PubMed1985

Diagnostic value of the fibrosis of the terminal hepatic venule in fatty liver and chronic hepatitis due to ethanol or other aetiology.

The frequency of fibrosis of the terminal hepatic venule (FTHV) has been investigated by two observers unaware of the patient's history, in needle biopsy specimens showing normal histology (n = 23), alcoholic steatosis (n = 23), steatosis in diabetes or overweight (n = 26), alcoholic hepatitis (n = 21), or virus-related chronic active hepatitis (n = 44). FTHV was coded following a scale from 0 to 3 of severity. Minimal (grade 1) FTHV was seen in most venules of biopsies with a normal histological pattern, and was considered a normal feature. Grade 2 of FTHV was absent in the group showing normal histology but was evident in 17.4%-39.7% of the venules observed in the other groups without attaining diagnostic relevance. The percentage rate of severe (grade 3) FTHV was 0.0, 4.9, 6.6, 18.7 and 2.9 in the respective groups as delineated above. In alcoholic hepatitis, severe FTHV therefore showed a higher frequency than in virus-related chronic hepatitis (p less than 0.001), with high values of sensitivity (0.75), specificity (0.93), and predictivity (0.84 positive, 0.98 negative) for ethanol aetiology. The ethanol-related diagnostic value of FTHV however, was low in steatosis.

Diagnosis, Differential↗
PubMed1995

The measurement of permeability in single rat venules using the red cell microperfusion technique.

The red cell microperfusion-micro-occlusion technique has been used to measure fluid filtration and reabsorption (Jv/A) at known microvascular pressures (Pc) in single mesenteric venules of anaesthetized rats. The relation between Jv/A and Pc is linear over the range of Pc from 15 to 50 cmH2O and its slope is the hydraulic permeability, Lp. Reproducible estimates of Lp can be made in the same venule in separate microperfusions. The value of Pc at Jv/A = 0 varies linearly with perfusate oncotic pressure and is the effective oncotic pressure of the perfusate, sigma delta pi, when the hydrostatic pressure in the pericapillary fluid is zero. The mean value for Lp (+/- S.E.M.) in forty venules was 2.43 (+/- 0.2) x 10(-7) cm s-1 cmH2O-1. Two potential errors of the micro-occlusion technique (vessel distensibility and marker red cell size) were investigated. It was found that the effects of vessel distensibility had little effect on red cell movements at times later than 2 s after a step change in Pc. Red cell size had a potentially large effect on estimates of the absolute values of Lp. Cooling the mesenteric tissues from 37 to 7 degrees C reduced Lp in proportion to the change in the reciprocal of water viscosity with temperature. Rat venular permeability was shown to be sensitive to histamine, with Lp increasing and sigma delta pi falling in a concentration-dependent fashion with histamine concentrations of 1.6 x 10(-5) to 3.3 x 10(-4) mol l-1 in the perfusate.

Animals↗
PubMed1983

Comparison of membrane electrical activity of cat gastric submucosal arterioles and venules.

Intracellular electrical recordings were made from arterioles and venules of the cat gastric submucosa. Spontaneous rhythmic fluctuations of the membrane potential were recorded in 54% of the venular preparations. Arteriolar cells showed no spontaneous activity. Excitatory junction potentials were recorded in arterioles but not venules after single shocks to the perivascular nerves. The amplitude of the excitatory junction potential was decreased in the presence of alpha-blockers. Repetitive stimulation of the perivascular nerve caused a biphasic electrical response of venular smooth muscle cells. The depolarizing component was decreased by alpha-adrenergic blockade and the hyperpolarizing component by beta-blockade. Venules contracted in response to smaller depolarizations than did arterioles. The voltage threshold for contraction of venular cells was similar to that for arteriolar cells but the venular cells were significantly more depolarized at rest than were the arteriolar cells. The difference in resting potential provides an explanation for the difference in sensitivity to electrical input.

Action Potentials↗
PubMed1992

Indomethacin-induced leukocyte adhesion in mesenteric venules: role of lipoxygenase products.

Although the pathogenetic mechanisms underlying indomethacin-induced mucosal injury remain undefined, the results from recent studies suggest that leukocyte adherence in gastric microvessels may be an important component of this injury process. The objective of this study was to determine whether clinically relevant plasma concentrations of indomethacin promote leukocyte-endothelial cell adhesive interactions in postcapillary venules. Erythrocyte velocity, vessel diameter, leukocyte rolling velocity, and the number of adherent (stationary for greater than or equal to 30 s) and emigrated leukocytes were measured in rat mesenteric venules. Repeat measurements of all parameters were obtained within 20 min after addition of either 2.5 or 25 micrograms/ml indomethacin to the mesenteric superfusate. In some experiments, rats were pretreated with either a leukotriene (LT) synthesis inhibitor (L 663,536), an LTD4 (MK-571) or LTB4 (SC 41930) receptor antagonist, misoprostol, or prostacyclin (PGI2). Indomethacin alone increased the number of adherent leukocytes, reduced both leukocyte rolling velocity and venular shear rate, but did not promote leukocyte emigration. L 663,536 and SC 41930 prevented all of the adhesive and hemodynamic alterations induced by indomethacin; misoprostol and PGI2, but not MK-571, exerted similar beneficial effects. These results indicate that indomethacin promotes leukocyte adherence in postcapillary venules through an LTB4-dependent mechanism.

Animals↗
PubMed1997

Neutrophil margination and extravasation in sinusoids and venules of liver during endotoxin-induced injury.

Neutrophils contribute to liver damage during endotoxin shock. The objective of this investigation was to document where neutrophils localize in the hepatic vasculature and whether they migrate out of sinusoids or postsinusoidal venules. A well-characterized model of galactosamine and endotoxin shock and immunostaining for neutrophil-associated migration inhibition factor-related protein complex 8/14 S100 calcium-binding proteins were used. Treatment of C3Heb/FeJ mice with 100 micrograms/kg Salmonella abortus equi endotoxin alone or in combination with 700 mg/kg galactosamine induced a time-dependent increase of neutrophil margination in sinusoids and postsinusoidal venules at 4 h. The number of venular neutrophils decreased in both groups at later time points without evidence for transmigration. Extravasation of neutrophils was only observed from sinusoids in galactosamine plus endotoxin-treated animals between 4 and 7 h, which correlated with parenchymal cell injury. After endotoxin alone, large numbers of neutrophils remained sequestered in sinusoids without injury. These data suggest that neutrophils cause hepatocellular injury during endotoxemia after extravasation and are less likely to cause damage when sequestered in the vasculature. In the liver, neutrophils migrate out of sinusoids and not out of postsinusoidal venules.

Animals↗
PubMed2005

Sphingosine 1-phosphate prevents platelet-activating factor-induced increase in hydraulic conductivity in rat mesenteric venules: pertussis toxin sensitive.

Sphingosine 1-phosphate (S1P) is a biologically active lipid. In vitro, S1P tightens the endothelial barrier, as assessed by a rapid increase in electrical resistance and a decrease in solute permeability. We hypothesized that this activity of S1P would also occur in vivo. Hydraulic conductivity (Lp), an assessment of endothelial barrier function, was measured in individually perfused venules in rat mesenteries. S1P (1 microM) decreased basal Lp by 63% when basal Lp was between 3.6 and 4.1 x 10(-7) cm x s(-1) x cmH2O(-1) but showed no effect when basal Lp was below 2 x 10(-7) cm x s(-1) x cmH2O(-1). Under either condition, S1P blocked the sixfold increase in Lp induced by platelet-activating factor (PAF, 10 nM). Perfusion of venules with pertussis toxin (0.1 microg/ml), a specific inhibitor of the inhibitory G protein, Gi, for 3 h did not affect basal Lp or the increased Lp induced by PAF. Pertussis toxin, however, significantly attenuated the inhibitory action of S1P on the PAF-induced increase in Lp, indicating the involvement of the Gi protein. Measurement of endothelial cytoplasmic Ca2+ concentration ([Ca2+]i) in venules loaded with fura-2 AM showed that S1P alone transiently increased basal endothelial [Ca2+]i (from 89 nM to 193 nM) but had no effect on the magnitude and time course of the PAF-induced increase in endothelial [Ca2+]i. These results indicate that S1P functions in vivo to prevent the PAF-induced increase in microvessel permeability. The inhibitory action of S1P involves the pertussis toxin-sensitive Gi protein and is not mediated by prevention of the PAF-induced increase in endothelial [Ca2+]i.

Animals↗
PubMed2006

TNF-alpha activation of arterioles and venules alters distribution and levels of ICAM-1 and affects leukocyte-endothelial cell interactions.

The observation that leukocyte-endothelial cell (EC) interactions are localized to specific regions on the microvessel wall suggests that adhesion molecule distribution is not uniform. We investigated ICAM-1 distribution and leukocyte-EC interactions in blood-perfused microvessels (<80 mum) in cremaster muscle of anesthetized mice, using intravital confocal microscopy and immunofluorescent labeling. Variability of ICAM-1 expression directly determines leukocyte adhesion distribution within the venular microcirculation and contributes to leukocyte rolling in arterioles during inflammation. The number of rolling interactions increased with ICAM-1 intensity (r(2) = 0.69, P < 0.05), and rolling velocity was lower in regions of higher ICAM-1 intensity. In controls, venular ICAM-1 expression was approximately twofold higher than in arterioles. After TNF-alpha treatment, ICAM-1 expression was significantly increased, 2.8 +/- 0.2-fold in arterioles and 1.7 +/- 0.2-fold in venules (P < 0.05). ICAM-1 expression on activated arteriolar ECs only reached the level of control venular ICAM-1. Arteriolar but not venular ECs underwent redistribution of ICAM-1 among cells; some cells increased and some decreased ICAM-1 expression, magnifying the variability of ICAM-1. TNF-alpha treatment increased the length of bright fluorescent regions per unit vessel length (42%, control; 70%, TNF-alpha) along the arteriolar wall, whereas no significant change was observed in venules (60%, control; 63%, TNF-alpha). The spatial distribution and expression levels of adhesion molecules in the microcirculation determine the timing and placement of leukocyte interactions and hence significantly impact the inflammatory response. That arteriolar ECs respond to TNF-alpha by upregulation of ICAM-1, although in a different way compared with venules, suggests an explicit role for arterioles in inflammatory responses.

Animals↗
PubMed2005

Angiopoietin-1 decreases plasma leakage by reducing number and size of endothelial gaps in venules.

Angiopoietin-1 (Ang-1) is essential for remodeling of the primitive vascular plexus and recruitment of mural cells during embryonic development. In the adult vasculature, Ang-1 can reduce plasma leakage in inflammation, but the mechanism of this action is not well understood. In the present study, we determined the magnitude and cellular mechanism of the antileak effect of Ang-1 in the airways of mice. Intravenous injection of bradykinin resulted in leakage of fluorescent microspheres (diameter 25-1,000 nm) from tracheal venules. The leakage peaked in 3-4 min and resolved by 10 min. High-resolution confocal microscopy revealed the presence of focal gaps at intercellular junctions of leaky venules. Genetically engineered Ang-1*, delivered systemically by adenoviral transduction of the liver, reduced leakage of 500-nm microspheres after bradykinin by 69%. The reduction in leakage coincided with a decrease in number and size of endothelial gaps. The proportion of venular surface occupied by endothelial gaps decreased 61%. Microsphere leakage correlated strongly with gap number and size (r2 = 0.89). Together the results suggest that Ang-1 reduces leakage from inflamed venules by restricting the number and size of gaps that form at endothelial cell junctions through effects on intracellular signaling, cytoskeleton, and junction-related molecules.

Angiopoietin-1↗
PubMed2004

Aggregate formation of erythrocytes in postcapillary venules.

The purpose of the present study was to obtain information on erythrocyte aggregate formation in vivo. The movements of erythrocytes in postcapillary venules of the rat spinotrapezius muscle at various flow rates were recorded with a high-speed video camera before and after infusion of dextran 500. To distinguish aggregates, the following criteria were used: 1) a fixed distance (4 microm) between the center points of two adjacent cells, 2) lack of visible separation between the adjacent cells, and 3) movement of the adjacent cells in the same direction. Without dextran 500 infusion, 11 and 5% of erythrocytes formed aggregates in low (33.2 +/- 28.3 s) and high pseudoshear (144.2 +/- 58.3 s) conditions, respectively, based on the above criteria. After dextran 500 infusion, 53% of erythrocytes satisfied the criteria in the low pseudoshear condition (26.5 +/- 17.0 s) and 13% of erythrocytes met the criteria in the high pseudoshear condition (240.0 +/- 85.9 s), indicating erythrocyte aggregation is strongly associated with shear rate. Approximately 90% of aggregate formation occurred in a short time period (0.15-0.30 s after entering the venule) in a region 15 to 30 microm from the entrance. The time delay may reflect rheological entrance conditions in the venule.

Animals↗
PubMed1993

Permeability to albumin in isolated coronary venules.

This study reports measurements of albumin permeability in isolated coronary venules. The isolated microvessel technique allows the quantification of transmural exchange of macromolecules under tightly controlled physical and chemical conditions. Transvenular exchange of albumin was studied in isolated coronary venules during alterations in filtration rate caused by changes in intravascular pressure. The apparent permeability coefficient of albumin (Pa) at an intraluminal pressure of 11 cmH2O was 3.92 +/- 0.43 x 10(-6) cm/s. Elevating intraluminal pressure to 16 and 21 cmH2O increased Pa to 5.13 +/- 0.57 x 10(-6) and 6.78 +/- 0.66 x 10(-6) cm/s, respectively. Calculation of the true diffusive permeability coefficient of albumin (Pd) at zero filtration rate was 1.54 x 10(-6) cm/s. The product of hydraulic conductance (Lp) and (1 - sigma), where sigma is the solute reflection coefficient, was 3.25 x 10(-7) cm.s-1 x cmH2O-1. At a net filtration pressure of 4-5 cmH2O, diffusion accounts for > 60% of total albumin transport across the venular wall. Transmural albumin flux is very sensitive to filtration rate, rising 6.7% for each cmH2O elevation of net filtration pressure. At 11 cmH2O net filtration pressure, convection accounts for nearly 70% of net albumin extravasation from the venular lumen. We suggest that the isolated coronary venule is a suitable preparation for the study of solute exchange in the heart.

Animals↗
PubMed1994

Histamine can induce leukocyte rolling in rat mesenteric venules.

Rolling is a retarded movement of leukocytes that depends on the function of the selectin class of adhesion molecules. In venules of internal organs, rolling is rapidly induced on tissue exposure by unknown mediator(s). Rolling was investigated with intravital microscopy in venules of the exteriorized mesentery of anesthetized rats. Immediately after exteriorization, rolling leukocyte flux was very low (10 +/- 4 min-1) and increased rapidly to reach a peak of 76 +/- 10 min-1 at 30 min. Intraperitoneal pretreatment of rats with histamine induced near-maximal rolling in mesenteric venules immediately after exteriorization. Leukocyte rolling was significantly inhibited by intravenular microinfusion of monoclonal antibody PB1.3 that recognizes and functionally blocks human and rat P-selectin. The effect of histamine was blocked by pretreatment with ranitidine, an H2-receptor antagonist, but not with diphenhydramine, which blocks H1 receptors. However, ranitidine did not block the subsequent increase of rolling leukocyte flux, and rolling leukocyte flux was similar in all groups 20 min after exteriorization. Histological investigation revealed degranulation of mast cells, suggesting release of histamine and other mediators. These findings indicate that histamine can induce leukocyte rolling in vivo via H2 receptors, most likely by inducing endothelial expression of P-selectin. In addition, mediators other than histamine released from mast cells and/or other cells are likely to promote sustained rolling.

Animals↗
PubMed1995

Changes in endothelial actin cytoskeleton in venules with time after histamine treatment.

In this study the time course of development and recovery of histamine-induced venular leaks was followed in conjunction with rearrangement of endothelial actin fibers. The microvasculature of a single mesenteric window of anesthetized Sprague-Dawley rats was perfused with buffered saline, with or without 10(-4) M histamine, for 3-30 min. Fluorescein isothiocyanate (FITC)-albumin was added for the last 3 min. The microvasculature was perfusion fixed, stained with rhodamine phalloidin (for filamentous actin), and viewed using confocal microscopy. The number and relative size of FITC-albumin leaks per venule length were measured. After 3 min of histamine application focal leaks appeared in some of the venules. Most focal leaks were accompanied by local breaks in the endothelial peripheral actin rim. Larger leaks were also present, accompanied by greater disruption of the venular endothelial peripheral actin rim, diffuse F-actin staining, and adherent platelets and leukocytes. Few central actin fibers were visible even in endothelial cells associated with large leaks. After 10-15 min of histamine exposure, larger leaks were more abundant but with fewer adherent cells. Central actin fibers in endothelial cells increased in number, peaking after 20 min of histamine, while the diffuse actin staining declined. Leak area per micrometer of venule peaked at 10-15 min, but the numbers of leaks per micrometer did not vary significantly from 3 to 30 min. These data suggest that the central fibers are not involved with the phase of increasing permeability, but they may play a role in the structural and functional recovery of endothelial cells perturbed by histamine.

Actins↗