Leukocyte adherence to venular endothelium during ischemia-reperfusion

1989 ◽  
Vol 257 (5) ◽  
pp. G683-G688 ◽  
Author(s):  
D. N. Granger ◽  
J. N. Benoit ◽  
M. Suzuki ◽  
M. B. Grisham
Keyword(s):  
Blood Flow ◽  
Superoxide Dismutase ◽  
Xanthine Oxidase ◽  
Ischemia Reperfusion ◽  
Vessel Diameter ◽  
Leukocyte Rolling ◽  
Ischemia And Reperfusion ◽  
Leukocyte Adherence ◽  
Rolling Velocity ◽  
Ischemic Intestine

Xanthine oxidase-derived oxidants and leukocytes have been implicated in the microvascular injury associated with reperfusion of ischemic intestine. The objective of this study was to determine whether xanthine oxidase-derived oxidants play a role in the leukocyte-microvascular interactions initiated by ischemia-reperfusion. Adherence and extravasation of leukocytes were monitored in cat mesenteric venules subjected to 1 h of ischemia (blood flow reduced to 20% of control) and reperfusion. Leukocyte rolling velocity, vessel diameter, and red cell velocity were also measured in control (untreated) animals and in animals pretreated with either allopurinol or superoxide dismutase. The responses of venular blood flow, wall shear rate, and leukocyte rolling velocity to ischemia and reperfusion did not differ between the three experimental groups. In control animals, 1 h of ischemia was associated with significant adherence and extravasation of leukocytes with reperfusion greatly enhancing these responses. Allopurinol treatment did not alter the responses to ischemia per se, yet it largely prevented the further increment in adherence and extravasation associated with reperfusion. Superoxide dismutase treatment attenuated the leukocyte responses elicited by both ischemia and reperfusion. Our observations that both allopurinol and superoxide dismutase attenuate reperfusion-induced leukocyte adherence and extravasation are consistent with the hypothesis that xanthine oxidase-derived oxidants initiate the leukocyte infiltration induced by reperfusion of ischemic intestine.

Role of platelet-activating factor in ischemia/reperfusion-induced leukocyte adherence

1990 ◽  
Vol 259 (2) ◽  
pp. G300-G305 ◽  
Author(s):  
P. Kubes ◽  
G. Ibbotson ◽  
J. Russell ◽  
J. L. Wallace ◽  
D. N. Granger
Keyword(s):  
Blood Flow ◽  
Ischemia Reperfusion ◽  
Platelet Activating Factor ◽  
Vessel Diameter ◽  
Control Group ◽  
Leukocyte Adherence ◽  
Adhesive Interaction ◽  
Microvascular Endothelium ◽  
Rolling Velocity ◽  
Web 2086

The objective of this study was to determine whether platelet-activating factor (PAF) mediates the leukocyte-endothelial cell interactions elicited by ischemia/reperfusion. The rates of adherence and extravasation of leukocytes were monitored in cat mesenteric venules subjected to 60 min of ischemia (blood flow reduced to 20% of control) followed by 60 min of reperfusion. Leukocyte rolling velocity, red blood cell velocity, and vessel diameter were also measured. The experiments were performed in control (untreated) animals and in animals pretreated with one of two PAF receptor antagonists, i.e., BN 52021 or WEB 2086. The responses of venular blood flow, wall shear rate, and vessel diameter did not differ between the three groups. In the control group, 1 h of ischemia was associated with significant adherence and extravasation of leukocytes, with reperfusion greatly enhancing these responses. The rates of leukocyte adherence and extravasation during reperfusion were greatly attenuated by both PAF antagonists. Furthermore, the proportion of adherent leukocytes that ultimately extravasate during reperfusion was markedly reduced by WEB 2086. These results suggest that PAF plays an important role in mediating the adhesive interaction between circulating leukocytes and microvascular endothelium induced by ischemia/reperfusion and that the phospholipid promotes the leukocyte extravasation associated with ischemia/reperfusion.

Leukocyte adhesion in local versus hemorrhage-induced ischemia

1992 ◽  
Vol 263 (3) ◽  
pp. H810-H815 ◽  
Author(s):  
M. A. Perry ◽  
D. N. Granger
Keyword(s):  
Endothelial Cell ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Rolling Velocity ◽  
Local Ischemia ◽  
Cell Adhesive ◽  
Local Restriction ◽  
Adhesive Interactions

The objective of this study was to compare the leukocyte-endothelial cell adhesive interactions elicited in postcapillary venules by either local ischemia-reperfusion or hemorrhage-reperfusion. Leukocyte rolling, adherence, and emigration were monitored in cat mesenteric venules exposed to an 85% reduction in blood flow (induced by either hemorrhage or local restriction of arterial inflow) for 1 h, followed by 1 h reperfusion. Leukocyte-endothelial cell interactions, venular diameter, and red blood cell velocity were measured during baseline, ischemia, and reperfusion periods. Both local and hemorrhage-induced ischemia reperfusion caused a reduction in leukocyte rolling velocity and increases in leukocyte adherence and emigration. Quantitatively, the adherence and emigration responses in both ischemia models were nearly identical. However, the two models differed in their response to immunoneutralization of the leukocyte adhesion glycoprotein CD11/CD18 with monoclonal antibody (MAb) IB4. The MAb had a more profound effect in attenuating leukocyte adherence and emigration in the local ischemia model. These results indicate that different factors may contribute to leukocyte-endothelial cell adhesive interactions observed in local vs. systemic models of ischemia-reperfusion.

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

1992 ◽  
Vol 262 (5) ◽  
pp. G903-G908 ◽  
Author(s):  
H. Asako ◽  
P. Kubes ◽  
J. Wallace ◽  
T. Gaginella ◽  
R. E. Wolf ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Plasma Concentrations ◽  
Mucosal Injury ◽  
Vessel Diameter ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Synthesis Inhibitor ◽  
Rolling Velocity ◽  
Beneficial Effects ◽  
Adhesive Interactions

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.

scholarly journals Xanthine oxidase and neutrophil infiltration in intestinal ischemia

1986 ◽  
Vol 251 (4) ◽  
pp. G567-G574 ◽  
Author(s):  
M. B. Grisham ◽  
L. A. Hernandez ◽  
D. N. Granger
Keyword(s):  
Superoxide Dismutase ◽  
Xanthine Oxidase ◽  
Reduced Glutathione ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Neutrophil Infiltration ◽  
Mucosal Injury ◽  
Ischemia And Reperfusion ◽  
Reactive Oxygen Metabolites ◽  
Oxygen Metabolites

A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radical may mediate the mucosal injury produced by reperfusion of ischemic intestine. Xanthine oxidase has been proposed as the primary source of these reduced O2 species because pretreatment with xanthine oxidase inhibitors such as allopurinol or pterin aldehyde prevent postischemic mucosal injury. Another potential source of oxygen radicals is the inflammatory neutrophil. To ascertain whether neutrophils could play a role in the pathogenesis of ischemia-reperfusion injury in the small bowel we examined the effect of ischemia and reperfusion on neutrophil infiltration and tissue levels of reduced glutathione, superoxide dismutase, and catalase. Our studies demonstrate that reperfusion of ischemic intestines results in a dramatic increase (1,800%) in neutrophil infiltration and a concurrent loss of reduced glutathione and superoxide dismutase of 60 and 30%, respectively. Catalase activity was unaffected by ischemia-reperfusion. Pretreatment with allopurinol or administration of superoxide dismutase prevented the influx of neutrophils and retarded the drop in reduced glutathione levels. These results suggest a relationship among xanthine oxidase-generated oxy radicals, neutrophil extravasation, and mucosal damage. We propose that ischemia and reperfusion results in xanthine oxidase-generated, superoxide-dependent accumulation of inflammatory neutrophils in the mucosa where neutrophil-derived reactive oxygen metabolites mediate and/or exacerbate intestinal injury.

Factors Influencing Leukocyte Adherence in Microvessels

1977 ◽  
Vol 38 (04) ◽  
pp. 0823-0830 ◽  
Author(s):  
Mayrovttz N. Harvey ◽  
Wiedeman P. Mary ◽  
Ronald F. Tuma
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Tissue Injury ◽  
Threshold Value ◽  
In Vivo Studies ◽  
Leukocyte Adherence ◽  
Rolling Velocity ◽  
Subsequent Behavior ◽  
Flow Stasis

SummaryIn vivo studies of the microcirculation of an untraumatized and unanesthetized animal preparation has shown that leukocyte adherence to vascular endothelium is an extremely rare occurrence. Induction of leukocyte adherence can be produced in a variety of ways including direct trauma to the vessels, remote tissue injury via laser irradiation, and denuding the epithelium overlying the observed vessels. The role of blood flow and local hemodynamics on the leukocyte adherence process is quite complex and still not fully understood. From the results reported it may be concluded that blood flow stasis will not produce leukocyte adherence but will augment pre-existing adherence. Studies using 2 quantitative measures of adherence, leukocyte flux and leukocyte velocity have shown these parameters to be affected differently by local hemodynamics. Initial adherence appears to be critically dependent on the magnitude of the blood shear stress at the vessel wall as evidenced by the lack of observable leukocyte flux above some threshold value. Subsequent behavior of the leukocytes as characterized by their average rolling velocity shows no apparent relationship to shear stress but, for low velocities, may be related to the linear blood velocity.

Beneficial actions of superoxide dismutase and catalase in stunned myocardium of dogs

1986 ◽  
Vol 250 (3) ◽  
pp. H372-H377 ◽  
Author(s):  
G. J. Gross ◽  
N. E. Farber ◽  
H. F. Hardman ◽  
D. C. Warltier
Keyword(s):  
Blood Flow ◽  
Superoxide Dismutase ◽  
Free Radicals ◽  
Oxygen Free Radicals ◽  
Ischemia Reperfusion ◽  
Free Radical Scavengers ◽  
Stunned Myocardium ◽  
Regional Myocardial Blood Flow ◽  
Control Group ◽  
Myocardial Segment

Recent evidence suggests that oxygen free radicals may partially mediate irreversible ischemia-reperfusion injury in the myocardium. In the present study, the effect of a combination of two oxygen free radical scavengers, superoxide dismutase plus catalase (SOD + CAT), on the recovery of subendocardial segment function following 15 min of coronary artery occlusion followed by 3 h of reperfusion ("stunned" myocardium) was compared with a control group in barbital-anesthetized dogs. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic areas was measured by sonomicrometry and regional blood flow by radioactive microspheres. SOD and CAT were infused into the left atrium 30 min before and throughout the occlusion period. Compared with the control group, %SS in the subendocardium of the ischemic region was significantly (P less than 0.05) greater in the SOD plus CAT-treated group during occlusion and throughout reperfusion. Since there were no significant differences in hemodynamics or regional myocardial blood flow between the SOD plus CAT and the control groups, these results suggest that toxic oxygen free radicals may be partially involved in the reversible ischemic injury that occurs during short periods of coronary occlusion followed by reperfusion.

Molecular determinants of lipid mediator-induced leukocyte adherence and emigration in rat mesenteric venules

1994 ◽  
Vol 266 (3) ◽  
pp. H847-H853 ◽  
Author(s):  
B. J. Zimmerman ◽  
J. W. Holt ◽  
J. C. Paulson ◽  
D. C. Anderson ◽  
M. Miyasaka ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Platelet Activating Factor ◽  
Leukotriene B4 ◽  
Intercellular Adhesion Molecule ◽  
Lipid Mediator ◽  
Leukocyte Rolling ◽  
Leukocyte Adherence ◽  
Intercellular Adhesion Molecule 1 ◽  
Rolling Velocity ◽  
Molecular Determinants

The objective of this study was to identify the molecular determinants of leukocyte rolling, adherence, and emigration elicited in postcapillary venules by the lipid mediators leukotriene B4 (LTB4) or platelet-activating factor (PAF). Leukocyte-endothelial cell adhesion and shear rate were monitored in rat mesenteric venules during superfusion with either LTB4 or PAF in the presence or absence of monoclonal antibodies (MAbs) directed against either leukocyte (CD18, CD11b) or endothelial cell [intercellular adhesion molecule 1 (ICAM-1), E-selectin, P-selectin] adhesion glycoproteins. In untreated animals and in animals receiving a nonbinding control MAb, LTB4 and PAF increased the number of both adherent (8- and 4-fold, respectively) and emigrated (14- and 8-fold, respectively) leukocytes, while reducing leukocyte rolling velocity (36 and 33%, respectively). The LTB4- and PAF-induced leukocyte adherence and emigration were significantly attenuated by pretreatment with MAbs directed against CD18, CD11b, ICAM-1, and E-selectin, but not P-selectin. The reduction in leukocyte rolling velocity induced by LTB4 was not affected by any of the MAbs; however, both P- and E-selectin MAbs significantly attenuated the reduction in leukocyte rolling velocity elicited by PAF. The results of this study indicate that the leukocyte adherence and emigration induced by both LTB4 and PAF are mediated by CD11b/CD18 on leukocytes and by ICAM-1 and E-selectin on endothelial cells. The molecular determinant of leukocyte rolling appears to be mediator specific, with the selectins mediating the rolling elicited by PAF.

Mucosal arachidonate metabolism and intestinal ischemia-reperfusion injury

1989 ◽  
Vol 257 (2) ◽  
pp. G299-G307 ◽  
Author(s):  
M. J. Mangino ◽  
C. B. Anderson ◽  
M. K. Murphy ◽  
E. Brunt ◽  
J. Turk
Keyword(s):  
Blood Flow ◽  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Leukotriene B4 ◽  
Time Dependent ◽  
Ischemia And Reperfusion ◽  
Synthesis Inhibitor ◽  
Intestinal Ischemia Reperfusion

Mucosal arachidonic acid metabolism was examined after 3 h of ischemia and 1 h of reperfusion in isolated ileal segments in the dog. The cyclooxygenase products thromboxane B2, 6-ketoprostaglandin F1 alpha, and prostaglandin E2 increased by 365%, 97%, and 158%, respectively, after ischemia and reperfusion but were not altered after 3 h of ischemia alone. The potent chemotactic lipoxygenase product leukotriene B4 (LTB4) increased by 687% after ischemia and reperfusion and was not affected by ischemia without reperfusion. In addition, tissue production of the thiol ether leukotrienes (LTC4, LTD4, and LTE4) increased threefold after ischemia and reperfusion. Quantitation of regionally isomeric hydroxy acids produced from arachidonate revealed a 300% increase in 12-hydroxyeicosatetraenoate (12-HETE) after intestinal ischemia and reperfusion without a change in other isomers (15-HETE and 5-HETE). Stereochemical analysis of 12-HETE demonstrated exclusive synthesis of the S-enantiomer. A significant and time-dependent decrease in intestinal blood flow also occurred during reperfusion. Administration of the dual cyclooxygenase-lipoxygenase synthesis inhibitor BW755C (1 mg/kg ia) did not alter time-dependent decreases in blood flow and failed to inhibit eicosanoid synthesis. Histologic examinations of intestinal samples revealed significant mucosal damage associated with ischemia alone and ischemia after reperfusion. This study indicates that intestinal ischemia-reperfusion injury is associated with dramatic alterations in mucosal production of vasoactive eicosanoids and with changes in blood flow that occur during reperfusion but not during ischemia alone. These events may be involved in the pathology characteristic of this injury.

Intestinal ischemia and reperfusion injury in transgenic mice overexpressing copper-zinc superoxide dismutase

1997 ◽  
Vol 273 (4) ◽  
pp. C1130-C1135 ◽  
Author(s):  
Devendra R. Deshmukh ◽  
Oleg Mirochnitchenko ◽  
Vikram S. Ghole ◽  
Doreen Agnese ◽  
Pritesh C. Shah ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Transgenic Mice ◽  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Myeloperoxidase Activity ◽  
Ischemia And Reperfusion ◽  
Intestinal Ischemia Reperfusion

Superoxide dismutase (SOD) scavenges oxygen radicals that are implicated in the pathogenesis of intestinal ischemia-reperfusion injury. The effect of intestinal ischemia and reperfusion was investigated in transgenic mice overexpressing human Cu-Zn SOD. Ischemia was induced by occluding the superior mesenteric artery. Myeloperoxidase activity was determined as an index of neutrophil infiltration, and malondialdehyde levels were measured as an indicator of lipid peroxidation. Forty-five minutes of intestinal ischemia followed by 4 h of reperfusion caused an increase in intestinal levels of malondialdehyde in both nontransgenic and transgenic mice, but the concentration of malondialdehyde was significantly greater in nontransgenic mice. Intestinal ischemia-reperfusion also caused an increase in intestinal and pulmonary myeloperoxidase activity in nontransgenic and transgenic mice, but the transgenic mice had significantly lower levels of myeloperoxidase activity than nontransgenic mice. Transgenic mice had higher levels of intestinal SOD activity than nontransgenic mice. There were no significant differences in the catalase or glutathione peroxidase activities. In conclusion, our study demonstrates that the overexpression of SOD protects tissues from neutrophil infiltration and lipid peroxidation during intestinal ischemia-reperfusion.

Adenosine inhibits ischemia-reperfusion-induced leukocyte adherence and extravasation

1989 ◽  
Vol 257 (5) ◽  
pp. H1334-H1339 ◽  
Author(s):  
M. B. Grisham ◽  
L. A. Hernandez ◽  
D. N. Granger
Keyword(s):  
Small Intestine ◽  
Ischemia Reperfusion ◽  
H2o2 Production ◽  
Leukocyte Adherence ◽  
Rolling Velocity ◽  
Microvascular Injury ◽  
Leukocyte Extravasation ◽  
Anti Inflammatory ◽  
Venular Endothelium

Ischemia and reperfusion (I/R) of the small intestine initiates a series of events that result in neutrophil-mediated microvascular injury. Recent reports suggest that adenosine possesses anti-inflammatory properties by virtue of its ability to inhibit neutrophil (PMN) superoxide (O2-.) and hydrogen peroxide (H2O2) production and to interfere with PMN adherence to cultured endothelium. In an attempt to further characterize the anti-inflammatory properties of adenosine in vivo we assessed the influence of exogenous adenosine on 1) I/R-induced PMN-mediated microvascular injury in the feline small intestine, 2) feline PMN superoxide production, and 3) I/R-induced PMN adherence to feline mesenteric venular endothelium. We found that intra-arterial administration of adenosine (2 microM) significantly attenuated the I/R-induced increases in intestinal capillary permeability. This protective effect of adenosine could not be explained entirely on its ability to inhibit PMN O2-. (or H2O2) production, since adenosine was effective in inhibiting feline PMN O2-. production by only 20%. Using intravital microscopic techniques in cat mesentery, we found that adenosine did not alter the responses of venular blood flow, shear rate, leukocyte rolling velocity, and leukocyte adherence to I/R when compared with control animals. However, the number of extravasated leukocytes during the ischemic period was significantly reduced by adenosine. Adenosine reduced the number of adherent leukocytes by 25% at 10 and 60 min of reperfusion while leukocyte extravasation was reduced by 65-70% during the same period. Our data indicate that the adenosine-induced suppression of leukocyte extravasation cannot be explained solely by an attenuation in leukocyte adherence to venular endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

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