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S Kanwar

Publications and source records attributed to S Kanwar.

At least 19 recordsLinked to original sources
PubMed2001

The role of Mac-1 (CD11b/CD18) in antigen-induced airway eosinophilia in mice.

Mac-1 (CD11b/CD18) is an important adhesion molecule involved in the migration of leukocytes, cell signaling, and subsequent secretory responses. Its precise role in eosinophil recruitment and activation in vivo is not entirely clear. We wished to directly examine the role of Mac-1 in eosinophil migration in a murine model of allergic pulmonary inflammation. Briefly, wild-type (C57Bl/6) and Mac-1-deficient/knockout (Mac-1 KO) mice were intraperitoneally sensitized with ovalbumin (OVA) and alum (AlOH) on Days 0 and 14, and intranasally challenged with OVA either once on Day 14 or five times on Days 14 and 25 through 28. Control animals were challenged with saline. Bronchial hyperresponsiveness was measured, bronchoalveolar lavage (BAL) fluid was collected, and lungs were harvested for histology 24 h after the last challenge. The data demonstrate that wild-type (WT) mice do not respond to one OVA challenge but do develop bronchial hyperreactivity and airway and tissue eosinophilia after five OVA challenges. Conversely, Mac-1 KO mice develop significant airway eosinophilia after one OVA challenge, and the degree of airway inflammation is comparable to that observed in allergic WT mice after five challenges. In Mac-1 KO mice, after five challenges, bronchial hyperreactivity and airway inflammation was significantly enhanced compared with their wild-type counterparts. Administration of an anti-Mac-1 antibody to WT mice, before each of five intranasal OVA challenges, significantly reduces the airway eosinophilia but has no effect on tissue eosinophilia or bronchial hyperresponsiveness. Intravenous injection of interleukin-5 induced a significant blood eosinophilia in both WT and Mac-1 KO mice. Intranasal eotaxin administration induced similar levels of eosinophil migration into the lung tissues and airways of both WT and Mac-1 KO mice. In conclusion, Mac-1-deficient mice develop enhanced eosinophilic inflammation in the lung in response to allergic antigen challenge.

Airway Resistance↗
PubMed2001

Protective effect of N-acetylcysteine in isoniazid induced hepatic injury in growing rats.

Status of oxidative/antioxidative profile was the mechanistic approach to inumerate the nature of protection by N-acetylcysteine (NAC) in isoniazid (INH) exposed experimental animals. Analysis of lipid peroxidation, thiol levels, cytochrome P450, superoxide dismutase (SOD), catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body and liver weight of animals and histological observations. Isoniazid exposure to animals resulted in no change in body and liver weights. Thiols, lipid peroxidation, catalase, SOD glutathione peroxidase, reductase, transferase and cytochrome P450 levels were altered with INH exposure. Supplementation of NAC with INH protected the animals against hepatotoxic reactions by minimizing the free radical induced tissue injury and overall maintenance of the endogenous scavengers of free radicals.

Acetylcysteine↗
PubMed2000

E/P-selectin-deficient mice: an optimal mutation for abrogating antigen but not tumor necrosis factor-alpha-induced immune responses.

Leukocyte recruitment in cremaster microcirculation was visualized by intravital microscopy, either in ovalbumin sensitized and challenged animals, or in response to TNF-alpha. In antigen-challenged mice a significant increase in leukocyte rolling (approximately 50 to 200-300 cells/min) and adhesion (2 to 15-20 cells/100 microm), and a very dramatic increase in emigration ( approximately 1 to >40 cells/field) was observed over 24 h. Although rolling and adhesion was dramatically blunted in P-selectin- or P selectin/ICAM-1-deficient mice, emigrated cell number was similar to that observed in wild-type mice. Leukocyte rolling, adhesion and emigration was almost entirely abrogated over 24 h in E/P-selectin-deficient mice, demonstrating that antigen-induced leukocyte recruitment can be entirely disrupted in the absence of both endothelial selectins. However, E/P-selectin-deficient mice were able to recruit leukocytes at 24 h after TNF-alpha challenge. Rolling 24 h post-TNF-alpha in E/P-selectin-deficient mice was not inhibitable with anti-L-selectin antibody, suggesting an entirely selectin-independent pathway of rolling. We identified this pathway to be alpha (4)-integrin dependent and demonstrated that VCAM-1 expression was increased only in mice challenged with TNF-alpha. These data demonstrate that, in vivo, sufficient amounts of TNF-alpha can recruit leukocytes independently of selectins, whereas inhibition of endothelial selectins is the optimal intervention in reducing the immune response to antigen.

Animals↗
PubMed2000

Lack of correlation between failure of gut barrier function and septic complications after major upper gastrointestinal surgery.

OBJECTIVE: To determine the influence of abnormal gut barrier function on the risk of septic complications in patients undergoing major resectional surgery for upper gastrointestinal cancer. SUMMARY BACKGROUND DATA: A failure of the gut mucosal barrier to exclude bacteria and endotoxin from the portal and systemic circulation is incriminated in the development of sepsis and multiple organ failure. Although the experimental data is compelling, corroborative evidence from studies in humans is sparse. This study attempted to correlate both preoperative gut barrier dysfunction and the pattern of change after surgery with septic outcome. METHODS: Sixty-eight patients undergoing curative resectional surgery for upper gastrointestinal cancer were monitored for 30-day septic morbidity (intraabdominal abscesses/empyema and pneumonia). Intestinal permeability, serum IgM and IgG anti-endotoxin antibodies (EndoCAb), and serum C-reactive protein were measured before surgery and on postoperative days 1 and 7. RESULTS: Increased intestinal permeability before surgery did not predict septic outcome. Major surgery was associated with increased intestinal permeability and evidence of endotoxin exposure. Comparing sepsis and nonsepsis groups, however, there was no significant difference in intestinal permeability, endotoxin exposure, and the acute phase response after surgery. CONCLUSIONS: This study demonstrates that gut barrier dysfunction occurs after surgery, but the magnitude of change does not differentiate patients in whom sepsis develops and those in whom it does not. Preoperative increased intestinal permeability had no predictive value for sepsis. This study failed to support the thesis that gut barrier dysfunction is directly linked to sepsis.

Acute-Phase Reaction↗
PubMed2000

Antiorthostatic suspension for 14 days does not diminish the oxidative response of neutrophils in mice.

The effects of long-term spaceflight on inflammatory responses have not been well-studied in either humans or animals. It is thus important to determine if the functions of immune and inflammatory cells are altered in models of spaceflight. One such animal model is antiorthostatic suspension (AOS), in which the experimental animal is subjected to a head-down tilt that mimics both the stress and the cephalad fluid shift experienced in spaceflight. A previous study reported that the peritoneal neutrophils from mice experiencing AOS generated less superoxide than unsuspended controls. We expanded on this study using several different stimuli and measuring the oxidative response of murine neutrophils in a variety of ways. These responses included the rate, lag period, and dose/response characteristics for superoxide generation, FACS analysis with dihydrodichlorofluorescein as a substrate, and a chemiluminescence response with luminol as a substrate. We also examined phagocytosis of three different microorganisms. While some effects of orthostatic suspension (attributable to the stress of the apparatus) were observed, no clear effects of AOS on oxidative function of the peritoneal neutrophils were seen.

Animals↗
PubMed1999

Overlapping roles for L-selectin and P-selectin in antigen-induced immune responses in the microvasculature.

Although L-selectin mediates lymphocyte attachment to endothelial venules of peripheral lymph nodes, its role in leukocyte recruitment into tissues following Ag challenge is less well established. The objective of this study was to systematically examine the role of L-selectin in leukocyte rolling in the peripheral microvasculature during the first 24 h of an immune response. A type I hypersensitivity response was elicited in wild-type (C57BL/6) and L-selectin-deficient mice by systemic (i.p.) sensitization and intrascrotal challenge with chicken egg OVA. The cremaster microcirculation was observed in untreated and sensitized mice 4, 8, and 24 h post-Ag challenge by intravital microscopy. Leukocyte recruitment in L-selectin-deficient mice and wild-type mice treated with an L-selectin function-blocking mAb was examined at each time point. Ag challenge induced a significant increase in leukocyte rolling (60 cells/min/venule to approximately 300 cells/min/venule) in wild-type mice at 4-24 h. This response was reduced by approximately 60-70% in L-selectin-deficient mice and in wild-type mice treated with an L-selectin-blocking mAb. P-selectin blockade by Ab completely inhibited leukocyte rolling at 4-24 h in wild-type animals and also blocked the residual rolling seen in L-selectin-deficient mice. Blocking E-selectin function had no effect on leukocyte rolling flux at any time point in wild-type or L-selectin-deficient mice. Despite reduced rolling, leukocyte adhesion and emigration were not measurably reduced in the L-selectin-deficient mice in this vascular bed. In conclusion, leukocyte rolling is L-selectin-dependent post-Ag challenge with L-selectin and P-selectin sharing overlapping functions.

Animals↗
PubMed1999

Varying roles of E-selectin and P-selectin in different microvascular beds in response to antigen.

Expression of E-selectin and P-selectin is critical in the effector phase of leukocyte recruitment in response to Ag. Whether their relative roles differ between tissues in response to the same Ag is unknown. In this study, a type I hypersensitivity response was elicited in C57BL/6 mice by systemic sensitization with OVA. Following local Ag challenge, endothelial selectin expression was examined in the skin and cremaster muscle microvasculature using a dual-radiolabeled mAb technique. Next, the dermal and muscle microcirculations were visualized using intravital microscopy to establish roles for P-selectin and/or E-selectin. In untreated mice, leukocyte recruitment in both skin and skeletal muscle was mediated entirely by P-selectin. Following Ag challenge, leukocyte rolling flux and adhesion were dramatically increased and leukocyte rolling velocity was unchanged in muscle. Only P-selectin expression increased in muscle, and leukocyte recruitment was entirely dependent upon this selectin. In contrast, in Ag-challenged skin, leukocyte rolling flux did not increase, but rolling velocity dropped profoundly. In skin, only E-selectin expression increased, and blockade of either E-selectin or P-selectin had minimal effect on either rolling flux or rolling velocity. Blockade of both selectins reduced rolling flux by 80% and increased rolling velocity sevenfold. These data highlight striking differences in expression of the endothelial selectins in separate microvascular beds in response to the same stimulus and demonstrate that these differences underlie very different patterns of leukocyte recruitment. The data underscore the importance of studying individual microvascular beds to understand tissue-specific leukocyte recruitment in vivo.

Animals↗
PubMed1998

Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis.

BACKGROUND: In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN). Poor outcome in acute pancreatitis is associated with a high incidence of systemic inflammatory response syndrome (SIRS) and sepsis. AIMS: To determine whether TEN can attenuate the acute phase response and improve clinical disease severity in patients with acute pancreatitis. METHODS: Glasgow score, Apache II, computed tomography (CT) scan score, C reactive protein (CRP), serum IgM antiendotoxin antibodies (EndoCAb), and total antioxidant capacity (TAC) were determined on admission in 34 patients with acute pancreatitis. Patients were stratified according to disease severity and randomised to receive either TPN or TEN for seven days and then re-evaluated. RESULTS: SIRS, sepsis, organ failure, and ITU stay, were globally improved in the enterally fed patients. The acute phase response and disease severity scores were significantly improved following enteral nutrition (CRP: 156 (117-222) to 84 (50-141), p < 0.005; APACHE II scores 8 (6-10) to 6 (4-8), p < 0.0001) without change in the CT scan scores. In parenterally fed patients these parameters did not change but there was an increase in EndoCAb antibody levels and a fall in TAC. Enterally fed patients showed no change in the level of EndoCAb antibodies and an increase in TAC. CONCLUSION: TEN moderates the acute phase response, and improves disease severity and clinical outcome despite unchanged pancreatic injury on CT scan. Reduced systemic exposure to endotoxin and reduced oxidant stress also occurred in the TEN group. Enteral feeding modulates the inflammatory and sepsis response in acute pancreatitis and is clinically beneficial.

APACHE↗
PubMed1998

Postischemic inflammation: a role for mast cells in intestine but not in skeletal muscle.

The objective of this study was to directly study a role for mast cells in ischemia-reperfusion (I/R)-induced mucosal and microvascular dysfunction. I/R was induced in the intestine and skeletal muscle (gastrocnemius and cremaster muscle) of wild-type mice and mast cell-deficient mice (W/Wv). Changes in mucosal permeability (blood-to-lumen clearance of 51Cr-EDTA), leukocyte infiltration (myeloperoxidase activity in the intestine and intravital microscopy in the cremaster muscle), and vascular permeability (tissue wet-to-dry weight ratio and FITC-albumin leakage) were measured as indexes of tissue dysfunction. In wild-type animals, intestinal I/R induced a significant increase in mucosal permeability, leukocyte infiltration, and vascular permeability. Mast cell-deficient animals were completely protected from I/R-induced mucosal dysfunction. However, skeletal muscle I/R induced a significant increase in leukocyte infiltration, FITC-albumin leakage, and edema formation to the same degree in both wild-type and mast cell-deficient animals. These data suggest that mast cells may be important mediators of I/R-induced mucosal and microvascular dysfunction in the intestine but not of microvascular dysfunction in skeletal muscle.

Animals↗
PubMed1998

An absolute requirement for P-selectin in ischemia/reperfusion-induced leukocyte recruitment in cremaster muscle.

OBJECTIVE: To systematically examine a role for P-selectin in a model of striated muscle ischemia/reperfusion (I/R). METHODS: Ischemia was induced in the cremaster muscle of mice by occluding the main feeding arteriole for 30 minutes. Blood flow was then restored to allow for 60 minutes of reperfusion and leukocyte kinetics were assessed during the control period (before I/R) and at 5, 30, and 60 minutes of reperfusion. To study a role for P-selectin in this model, three different approaches were used: Wild-type animals received fucoidin (10 mg/kg, i.v.), an anti-P-selectin antibody (RB40.34; 20 mg/animal, i.v.) at 25 minutes of ischemia, or I/R was induced in P-selectin-deficient mice. RESULTS: Ischemia/reperfusion induced a rapid and significant increase in leukocyte rolling, adhesion, and emigration in wild-type mice. The I/R-induced increase in leukocyte rolling was transient, inasmuch as it was reduced by approximately 50% at 30 minutes of reperfusion, and returned to control levels by 60 minutes. Both fucoidin and an anti-P-selectin antibody completely prevented the I/R-induced increase in leukocyte rolling. The P-selectin-deficient animals exhibited absolutely no baseline leukocyte rolling, adhesion, or emigration. Furthermore, I/R did not induce any increase in leukocyte recruitment in the P-selectin-deficient animals over the first 60 minutes of reperfusion. CONCLUSION: The results from this study clearly illustrate that P-selectin is absolutely critical in both baseline and I/R-induced leukocyte infiltration in the murine-striated muscle.

Animals↗
PubMed1997

The association between alpha4-integrin, P-selectin, and E-selectin in an allergic model of inflammation.

In this study, we examined the relationship between the endothelial selectins (P-selectin and E-selectin) and whether they are critical for alpha4-integrin-dependent leukocyte recruitment in inflamed (late phase response), cremasteric postcapillary venules. Animals were systemically sensitized and 2 wk later challenged intrascrotally with chicken ovalbumin. Leukocyte rolling flux, adhesion, and emigration were assessed at baseline and 4 and 8 h postantigen challenge. There was a significant increase in leukocyte rolling flux, adhesion, and emigration in sensitized and challenged mice at both 4 and 8 h. At 8 h, the increase in leukocyte rolling flux was approximately 50% inhibitable by an anti-alpha4-integrin antibody, 98% inhibitable by fucoidin (a selectin-binding carbohydrate), and 100% inhibitable by an anti-P-selectin antibody. P-selectin-deficient animals displayed no leukocyte rolling or adhesion at 8 h after challenge. However, at 8 h there were many emigrated leukocytes in the perivascular space suggesting P-selectin-independent rolling at an earlier time point. Indeed, at 4 h postantigen challenge in P-selectin-deficient mice, there was increased leukocyte rolling, adhesion, and emigration. The rolling in the P-selectin-deficient mice at 4 h was largely alpha4-integrin dependent. However, there was an essential E-selectin-dependent component inasmuch as an anti-E-selectin antibody completely reversed the rolling, and in E-selectin and P-selectin double deficient mice rolling, adhesion and emigration were completely absent. These results illustrate that P-selectin underlies all of the antigen-induced rolling with a brief transient contribution from E-selectin in the P-selectin-deficient animals. Finally, the antigen-induced alpha4-integrin-mediated leukocyte recruitment is entirely dependent upon endothelial selectins.

Animals↗
PubMed1996

Nitric oxide synthase activity in portal-hypertensive and cirrhotic rats.

BACKGROUND/AIMS: The hyperdynamic circulation of cirrhosis and portal hypertension has been postulated to be due to the vasodilatory effects of nitric oxide. However, studies using pharmacological inhibitors of nitric oxide synthase have yielded conflicting results. We aimed to measure nitric oxide synthase activity in tissues from two different rat models of cirrhosis and portal hypertension. METHODS: Cirrhosis was induced by chronic bile duct ligation, and prehepatic portal hypertension by portal vein stenosis. Controls were sham-operated. A fourth group was treated with lipopolysaccharide endotoxin. Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthase activity was assayed by measuring the conversion rate of 14C-arginine to 14C-citrulline in homogenates of stomach, jejunum, liver, kidney and aorta. RESULTS: Jejunal homogenates from the portal vein-stenosed rats showed a significant 10-fold elevation of Ca(2+)-dependent nitric oxide synthase activity. Cirrhotic rat kidney showed significantly decreased Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthase activity. Endotoxin treatment increased Ca(2+)-independent nitric oxide synthase activity in jejunum and liver. There was no increase in Ca(2+)-independent nitric oxide synthase activity in any tissues from cirrhotic or portal hypertensive rats. CONCLUSIONS: We conclude that the lack of increase in Ca(2+)-independent nitric oxide synthase activity does not support the hypothesis that nitric oxide is the major cause of hyperdynamic circulation in cirrhosis.

Animals↗
PubMed1996

Hydrogen peroxide induces leukocyte rolling: modulation by endogenous antioxidant mechanisms including NO.

In this study, intravital microscopy was used to examine the mechanisms that regulate H2O2-induced leukocyte rolling within rat mesenteric venules in vivo. H2O2 elicited leukocyte rolling within a narrow response window between 10 and 500 microM H2O2. Continuous superfusion with 100 microM H2O2 induced a large but transient increase in the flux of rolling leukocytes, whereas a short 5-min pulse elicited a sustained increase in rolling flux. Both treatments caused increases in leukocyte adhesion. H2O2-induced increases in leukocyte flux and adhesion could be prevented with an anti-P-selectin antibody. Inhibition of endogenous catalase (aminotriazole), glutathione (diethyl maleate), or nitric oxide (NG-nitro-L-arginine methyl ester) shifted the effective concentration of H2O2; continuous superfusion with 10 microM H2O2 now elicited large and sustained increases in leukocyte rolling flux, whereas 100 microM H2O2 elicited less than optimal responses. Dual antioxidant inhibition further reduced the effective H2O2 concentration to 1 microM H2O2. A nitric oxide donor prevented the increased rolling flux induced by 100 microM H2O2. These findings suggest that endogenous antioxidants are important regulators of H2O2-induced, P-selectin-dependent leukocyte rolling in vivo.

Animals↗
PubMed1995

Desmopressin induces endothelial P-selectin expression and leukocyte rolling in postcapillary venules.

Desmopressin, (DDAVP; 1-desamino-8-D-arginine vasopressin) increases the release and activity of von Willebrand factor (vWF); however, its effects on the other major constituent of endothelial Weibel-Palade bodies, P-selectin, has not been investigated. DDAVP-induced P-selectin expression may explain DDAVP's efficacy in bleeding disorders in which vWF levels are normal. Therefore, the objective of this study is to assess the effect of DDAVP on P-selectin expression on endothelial cells of postcapillary venules in vivo and on human umbilical vein endothelium in vitro, and to determine whether DDAVP has direct effects on leukocyte behavior in postcapillary venules. DDAVP (0.1 and 1.0 microgram/mL) induced a significant but transient increase in P-selectin expression on human umbilical vein endothelial cells as well as on rat and human platelets. Immunohistochemical analysis of rat postcapillary venules showed that in contrast to saline, DDAVP injection (1 microgram/kg, intravenous) induced significant endothelial P-selectin expression. DDAVP administration also induced a rapid and significant increase in leukocyte rolling in rat mesenteric venules in vivo. This response was entirely dependent on P-selectin, as an anti-P-selectin antibody rapidly reversed the DDAVP-induced increase in leukocyte rolling. DDAVP induced leukocyte rolling in medium (20 to 40 microns) and large (> 40 microns), but not small (< 20 microns), postcapillary venules. In animals that were treated with DDAVP, there was a steady and significant increase in leukocyte adhesion. This study shows that DDAVP can directly induce P-selectin expression on endothelium in vitro and in vivo and that the latter response is capable of supporting prolonged leukocyte rolling in rat postcapillary venules.

Animals↗
PubMed1995

Neutrophil adhesion is impaired in rat model of cholestasis.

BACKGROUND & AIMS: A high incidence of septic complications has been documented in patients with obstructive jaundice undergoing surgery. Because neutrophils play a central role in the response to infection, the aim of this study was to investigate neutrophil function in a rat model of acute cholestasis induced by bile duct resection. METHODS: Neutrophil function was assessed using both in vivo and in vitro techniques. RESULTS: The inflammatory response was defective in vivo in bile duct-resected (BDR) rats compared with sham-resected controls. Furthermore, proinflammatory stimulus-induced neutrophil adherence and emigration from mesenteric values, assessed in vivo using intravital microscopy, was attenuated in BDR vs. sham rats. Neutrophils isolated from BDR and sham rats studied in vitro adhered to a rat biological substratum similarly. However, stimulated neutrophil adherence was eliminated in the presence of BDR but not sham plasma. Similar findings were observed using plasma obtained from a patient with obstructive cholestasis. Experiments performed to further characterize this antiadhesive factor in BDR plasma suggest that the factor is probably a heat-stable glycoprotein. CONCLUSIONS: Cholestasis in the rat is associated with a defective acute inflammatory response that appears, at least in part, to be caused by a constituent of cholestatic plasma that is antiadhesive to neutrophils.

Acute Disease↗
PubMed1995

Leukotriene C4/D4 induces P-selectin and sialyl Lewis(x)-dependent alterations in leukocyte kinetics in vivo.

The objective of this study was to assess the effect of leukotriene C4 (LTC4) on the flux of rolling leukocytes, leukocyte rolling velocity, and leukocyte adhesion in postcapillary venules in vivo and to study the underlying molecular mechanisms involved. LTC4 (20 nmol/L) induced a rapid and significant increase in leukocyte rolling flux that was inhibitable by an anti-P-selectin antibody and soluble sialyl Lewis(x) (sLe(x)). LTC4 also induced a significant reduction in leukocyte rolling velocity, an event that was independent of P-selectin but entirely dependent on sLe(x). This LTC4-induced reduction in leukocyte rolling velocity was independent of any hemodynamic alterations. Another P-selectin effector, histamine, did not affect leukocyte rolling velocity even at > 5000 times the concentration of LTC4. Treatment with an anti-L-selectin antibody had no effect on the LTC4-induced increase in leukocyte rolling or reduction in rolling velocity. Inhibition of LTC4 bioconversion to LTD4 by pretreatment with L-serine (100 mumol/L) prevented the LTC4-induced increase in leukocyte rolling flux and the LTC4-induced reduction in leukocyte rolling velocity. A subtle, yet significant, increase in leukocyte adhesion was also observed with LTC4. Pretreatment with a platelet-activating factor receptor antagonist returned the LTC4-induced leukocyte rolling velocity to baseline levels. The addition of a very low concentration of platelet-activating factor (1 nmol/L) induced significant leukocyte adhesion in the presence of LTC4 but not histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Nitric oxide is an antiadhesive molecule for leukocytes.

There is growing evidence that nitric oxide (NO.), a biologically active gas continuously produced by endothelium, is a homeostatic regulator of leukocyte adhesion in the microcirculation. Inhibition of NO. production leads to increased leukocyte rolling and adhesion in various vascular beds and two adhesion molecules, P-selectin and CD11/CD18, have been implicated in these processes. The role of mast cells and mast cell-derived mediators as potential contributors to the increased adhesion are discussed in this review. Moreover, oxidants may initiate the leukocyte recruitment after NO. synthesis inhibition. Recent data demonstrating increased oxidative stress in endothelium deprived of NO. are summarized. The role of NO. as an anti-inflammatory and antiadhesive modulator in postischemic venules of various organs is also discussed. The beneficial effect of NO. donors in this inflammatory condition is summarized. Finally, the potential use of NO. donating drugs in concert with available pharmaceutical compounds to reduce inflammation is reviewed.

Animals↗