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J Appl Physiol 82: 913-917, 1997;
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Journal of Applied Physiology
Vol. 82, No. 3, pp. 913-917, March 1997
CELLULAR ASPECTS OF LUNG FUNCTION

Endogenous nitric oxide decreases xanthine oxidase-mediated neutrophil adherence: role of P-selectin

Lance S. Terada, John E. Repine, Dale Piermattei, and Brooks M. Hybertson

Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver, Colorado 80262

ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES

ABSTRACT

Terada, Lance S., John E. Repine, Dale Piermattei, and Brooks M. Hybertson. Endogenous nitric oxide decreases xanthine oxidase-mediated neutrophil adherence: role of P-selectin. J. Appl. Physiol. 82(3): 913-917, 1997.---The oxygen radical-producing enzyme xanthine oxidase (XO) can promote neutrophil adherence to endothelium. Recognizing that a balance often exists in inflammatory processes, we sought to determine whether XO initiates antiadherent pathways. We found that bovine pulmonary arterial endothelial cells (EC) exposed to XO released increased amounts of nitrite into the media, reflecting an increased production of nitric oxide (NO). When EC were subjected to shear stress, treatment with XO and/or the NO synthase inhibitor Nomega -nitro-L-arginine (L-NNA) increased neutrophil rolling behavior and firm neutrophil adherence to EC in an additive fashion. Both rolling and adherent interactions were abolished by monoclonal antibodies directed against P-selectin. In addition, treatment of EC with XO and/or L-NNA increased both surface expression of P-selectin and release of von Willebrand factor into media. Finally, treatment of EC with the NO donor sodium nitroprusside decreased XO-mediated neutrophil rolling and adherence. We conclude that XO stimulates EC to produce NO and that NO decreases the P-selectin-dependent neutrophil adhesion initiated by XO. Such increases in endogenous NO may constitute an important negative-feedback response to the acute proadhesive effects of XO.

endothelial cells; neutrophils; inflammation; multiple organ failure; acute respiratory disease syndrome

INTRODUCTION

CIRCULATING XANTHINE OXIDASE (XO), which is increased in patients with acute respiratory distress syndrome (6), may participate in the systemic activation of inflammatory cells, which is the signature event defining multiple organ failure. For instance, hepatic ischemia-reperfusion causes massive release of XO into the circulation and consequent lung injury (23). In addition, after intestinal ischemia-reperfusion, circulating XO levels increase and promote lung neutrophil retention (17). However, endogenous protective mechanisms that may be activated during such secondary pulmonary injury have not been well studied. Recently, we found that endogenous nitric oxide (NO) diminished lung injury and neutrophil recruitment after intestinal ischemia-reperfusion (20). We therefore hypothesized that exposure of endothelial cells (EC) to XO would stimulate the production of NO by EC, and NO, in turn, would diminish adhesive interactions between neutrophils and EC. In the present study, we demonstrate that EC stimulated with XO produce NO in an apparent negative-feedback cycle with respect to neutrophil adherence. The opposing effects of XO and NO on neutrophil adherence appear to be mediated through their disparate effects on P-selectin expression.

MATERIALS AND METHODS

Source of reagents. Sodium nitrite was obtained from Mallinckrodt (St. Louis, MO), blocking monoclonal antibody CLB-throm/6 against P-selectin from Monosan, and unconjugated and peroxidase-conjugated rabbit polyclonal antibodies to von Willebrand factor (vWF) from Dako (Carpinteria, CA). XO (grade III from bovine milk, 1.2 U/mg), superoxide dismutase (SOD; bovine erythrocyte, 3,000 U/mg), Nomega -nitro-L-arginine (L-NNA), sodium nitroprusside (SNP), and all other reagents were obtained from Sigma Chemical (St. Louis, MO).

Endothelial cell culture. Bovine pulmonary artery EC were harvested by using collagenase digestion, passaged twice in D-valine minimum essential medium (MEM) to minimize smooth muscle contamination, and cultured in Eagle's MEM with 10% fetal calf serum (18). EC were studied after 2-3 passages.

Nitrite release. Production of NO by EC was assessed by release of nitrite (5). EC were plated in 96-well enzyme-linked immunoabsorbent assay (ELISA) plates and grown to confluence. EC were washed twice with Hanks' balanced salt solution (HBSS) and exposed to 10 mU/ml XO, 200 µM hypoxanthine (HX), and 30 U/ml SOD and/or 200 µM L-NNA for 30 min at 37°C in a total volume of 200 µl HBSS/well. Media (50 µl) were removed and added to 50 µl Greiss reagent in a separate ELISA plate and incubated for 10 min at room temperature with shaking. The optical density at 540 nm was measured with a microplate reader (Bio-Tek EL 340, Winooski, VT) and compared with a standard curve of sodium nitrite in HBSS.

Neutrophil-EC dynamic interactions. Neutrophils were isolated from healthy human donors by Percoll gradient separation (18). EC were passaged into gelatin-coated glass capillary tubes 1.1 mm in internal diameter (Scientific Manufacturing Industries, Emeryville, CA). Fresh medium was flushed once through the tubes 4-5 h after seeding, and EC were grown overnight into confluent monolayers occupying approximately one-half of the internal surface of the tube. After treatment with 10 mU/ml XO, 200 µM HX, 200 µM L-NNA, 25 µM SNP, and/or 4 µg/ml anti-P-selectin antibodies for 30 min at 37°C, capillary tubes were secured to the stage of an inverted phase-contrast microscope (Nikon) with EC in the dependent position and kept at 37°. Neutrophils (2 × 105/ml in HBSS with 5% fetal calf serum) were infused by syringe pump at a constant flow rate. With the use of the Hagan-Poiselle equation (14), the shear rate was calculated to be 96 s-1. With the assumption of a viscosity of 0.0084 P at 37° (13), this corresponds to an approximate shear stress of 0.81 dyn/cm2. Neutrophil-EC interactions were recorded on VCR (Javelin, CA) for later playback analysis. The number of rolling neutrophils passing a standardized 500-µm bar and the number of firmly adherent (no movement for 30 s) neutrophils per 0.25 mm2 were determined for at least three random fields per tube.

P-selectin surface expression and vWF release. EC were grown to confluence in 96-well ELISA plates and then exposed to 10 mU/ml XO, 200 µM HX, and/or 200 µM L-NNA for 30 min at 37°C. EC were fixed with 1% paraformaldehyde and then washed twice with HBSS and blocked with 2% bovine serum albumin (BSA) in HBSS at 25°C for 30 min. After two subsequent washes, EC were incubated with anti-P-selectin (1:500 in 0.1% BSA) for 30 min at 37°C, washed twice, incubated with rabbit anti-mouse immunoglobulin G-peroxidase (1:1,000 in 0.1% BSA) for 20 min at 25°C, washed twice, and developed with o-phenylenediamine dihydrochloride. vWF release was measured by sandwich ELISA as previously described (7) with the use of unconjugated and peroxidase-conjugated antibodies at a 1:500 dilution and expressed as absorbance units.

Statistical analysis. Group means were analyzed by one-way analysis of variance with Student-Newman-Keuls multiple-group comparisons.

RESULTS

Effect of XO and L-NNA on nitrite release. Treatment of EC with HX and XO (HX+XO) increased (P < 0.01) release of nitrite into the media, compared with control EC (Fig. 1). Addition of SOD to prevent superoxide anion radical-mediated oxidation of NO to nitrate further increased nitrite release from HX+XO-treated EC (P < 0.001) compared with SOD-treated controls or HX+XO-treated EC not exposed to SOD. Addition of the NO syn- thase inhibitor L-NNA decreased nitrite levels (P < 0.001) released from HX+XO-treated EC exposed to SOD.
Fig. 1. Treatment of endothelial cells (EC) with xanthine oxidase (XO; 10 mU/ml) plus hypoxanthine (HX; HX+XO; 200 µM) increased release of nitrite into the media compared with control EC (* P < 0.01). Values are means ± SE; n = 12 individual determinations. EC treated with superoxide dismutase (SOD; 30 U/ml), XO, and HX had increased release of nitrite compared with EC treated with SOD alone or HX+XO alone (** P < 0.001). Nomega -nitro-L-arginine (L-NNA) (200 µM) decreased nitrite release from EC treated with SOD, XO, and HX (# P < 0.001). HBSS, Hanks' balanced salt solution.
[View Larger Version of this Image (12K GIF file)]

Effect of XO and L-NNA on neutrophil-EC interactions. Treatment of EC with either HX+XO or L-NNA increased the numbers of rolling (Fig. 2, P < 0.01) and adherent (Fig. 3, P < 0.05) neutrophils at a shear rate of 96 s-1 compared with untreated controls. In addition, treatment of EC with both HX+XO and L-NNA increased rolling (P < 0.001) and adherence (P < 0.05) compared with EC treated with either HX+XO or L-NNA alone. Cotreatment with antibodies against P-selectin decreased both rolling (P < 0.05) and adherence (P < 0.05) of neutrophils to baseline values in EC treated with HX+XO and/or L-NNA but did not alter rolling or firm adherence of neutrophils to untreated control EC (P > 0.05). Neutrophil rolling increased (P < 0.01) as early as 15 min into L-NNA exposure, although only at a lower shear rate of 38 s-1 (data not shown).
Fig. 2. Treatment of EC with either XO (10 mU/ml) plus HX (200 µM) or L-NNA (200 µM) increased the number of rolling neutrophils compared with untreated controls (open bars, filled bar; * P < 0.01). Values are means ± SE; n = 5-11 individual capillary tubes. Treatment of EC with both HX+XO and L-NNA increased neutrophil rolling compared with EC treated with either HX+XO or L-NNA alone (** P < 0.001). Cotreatment with antibodies against P-selectin (hatched bars) decreased neutrophil rolling in EC treated with HX+XO and/or L-NNA (# P < 0.05) but did not alter rolling in untreated control EC (P > 0.05). Neutrophil rolling in all groups treated with anti-P-selectin were not different from untreated controls (P > 0.05).
[View Larger Version of this Image (16K GIF file)]

Fig. 3. Treatment of EC with either XO (10 mU/ml) plus HX (200 µM) or L-NNA (200 µM) increased the number of firmly adherent neutrophils compared with untreated controls (* P < 0.05). Values are means ± SE; n = 5 individual capillary tubes. Treatment of EC with both HX+XO and L-NNA increased neutrophil adherence compared with EC treated with either HX+XO or L-NNA alone (** P < 0.05). Cotreatment with antibodies against P-selectin (hatched bars) decreased adherence to EC treated with HX+XO and/or L-NNA (# P < 0.05) but did not alter adherence to untreated control EC (P > 0.05). Neutrophil adherence in all groups treated with anti-P-selectin were not different from untreated controls (P > 0.05).
[View Larger Version of this Image (17K GIF file)]

Effect of XO and L-NNA on P-selectin surface expression and vWF release. Treatment of EC with HX+XO or L-NNA increased P-selectin surface expression (P < 0.001) compared with control EC (Fig. 4). Moreover, treatment of EC with both HX+XO and L-NNA further increased P-selectin surface expression relative to EC treated with either HX+XO or L-NNA alone (P < 0.001). Treatment of EC with HX+XO and/or L-NNA also increased release of vWF into media (P < 0.05) compared with control EC (Fig. 5). vWF levels after treatment of EC with both HX+XO and L-NNA were not significantly different (P > 0.05) from vWF levels observed after treatment of EC with either HX+XO or L-NNA alone.
Fig. 4. Treatment of EC with either XO (10 mU/ml) plus HX (200 µM) or L-NNA (200 µM) increased P-selectin surface expression compared with control EC (* P < 0.001). Values are means ± SE (n = 11 individual determinations) and are expressed as raw absorbance units. Treatment of EC with both HX+XO and L-NNA further increased P-selectin surface expression compared with EC treated with either HX+XO or L-NNA alone (** P < 0.001).
[View Larger Version of this Image (14K GIF file)]

Fig. 5. EC treated with XO (10 mU/ml) plus HX (200 µM) and/or L-NNA (200 µM) released more von Willebrand factor (vWF) into media than control EC (* P < 0.05). Values are means ± SE (n = 11 individual determinations) and are expressed as raw absorbance units. vWF levels after treatment of EC with both HX+XO and L-NNA were not significantly different (P > 0.05) from vWF levels observed after treatment of EC with either HX+XO or L-NNA alone.
[View Larger Version of this Image (12K GIF file)]

Effect of SNP on neutrophil rolling. Treatment of EC with HX+XO increased the number of rolling (P < 0.001) and firmly adherent (P < 0.01) neutrophils compared with untreated controls (Fig. 6). EC cotreated with both HX+XO and SNP supported less neutrophil rolling (P < 0.001) and firm neutrophil adherence (P < 0.05) compared with EC treated with HX+XO alone.
Fig. 6. A: treatment of EC with XO (10 mU/ml) and HX (200 µM) increased number of rolling neutrophils compared with untreated controls (* P < 0.001), whereas cotreatment of EC with both HX+XO and sodium nitroprusside (SNP; 25 µM) decreased neutrophil rolling compared with EC treated with HX+XO alone (# P < 0.001). B: treatment of EC with HX+XO increased number of firmly adherent neutrophils compared with untreated controls (* P < 0.001), whereas cotreatment of EC with both HX+XO and SNP decreased neutrophil adherence compared with EC treated with HX+XO alone (# P < 0.001).
[View Larger Version of this Image (18K GIF file)]

DISCUSSION

After injury to one organ, XO is released into the circulation and increases neutrophil sequestration in other organs (17). However, endogenous mechanisms that may be activated to limit the secondary spread of inflammation have not been studied. Recently, we observed that endogenous production of NO by the lung prevented pulmonary inflammation following mesenteric ischemia-reperfusion (20), suggesting a possible protective endothelial response against circulating XO. In the present study, we found that XO stimulated NO production by EC, and this enhanced NO generation caused a decrease in P-selectin-dependent neutrophil adhesion to EC.

We found first that XO increased L-NNA-inhibitable nitrite release from EC, consistent with an increased production of NO. The effect was relatively rapid, occurring within 30 min, consistent with activation of constitutive endothelial NO synthase (eNOS). Although the mechanism by which XO may activate eNOS is unclear, it is notable that XO increases cytosolic free calcium in EC (2) and induces vWF secretion from EC, a process that is also Ca2+ dependent (22).

The XO-stimulated release of NO appeared to partially counteract the proadhesive effects of XO because cotreatment of EC with L-NNA further increased neutrophil rolling behavior and adherence to XO-treated EC. In support of this interpretation, addition of the NO donor SNP decreased neutrophil rolling and adherence to XO-treated EC. These data are consistent with observations that exogenous administration of NO by NO donors decreases leukocyte adherence to XO-treated mesenteric venules (3). The situation may be similar to ischemic-reperfused tissues, although conflicting studies report that exogenous NO donors either decrease (4) or do not affect (9) leukocyte rolling in reperfused vessels. In the study of Gauthier et al. (4), however, the NO donor was given intravenously 10 min before reperfusion, whereas it was superfused just before reperfusion in the study of Kubes et al. (9). Notwithstanding, the effect of endogenously produced NO on oxidant-induced neutrophil adhesion has not previously been recognized, and this mechanism needs to be considered for its ability to alter neutrophil adhesion.

Treatment of EC with L-NNA alone also increased both neutrophil rolling and adherence, suggesting that basal production of NO by EC prevents excessive adhesion of neutrophils to uninjured endothelium. This correlates well with observations that NG-nitro-L-arginine methyl ester (L-NAME) increases leukocyte rolling (1) and adherence (10, 12) in mesenteric vessels within 30-60 min in vivo. In one study, lack of an effect of L-NAME on static neutrophil adherence in vitro in a similar time frame (16) may relate to the lack of shear stress, which rapidly induces NO release by EC (11).

NO decreased neutrophil-EC interactions, at least in part, by decreasing P-selectin expression. First, blocking monoclonal antibodies against P-selectin eliminated XO- and L-NNA-induced neutrophil rolling and adherence. The effect of anti-P-selectin on adherence may be explained by the requirement of rolling for firm adherence to occur at the shear rate studied in this system (19). Second, surface expression of P-selectin increased after treatment of EC with L-NNA and/or XO. P-selectin is a preformed glycoprotein that is stored in endothelial Weibel-Palade bodies. Accordingly, it is significant that treatment of EC with L-NNA and/or XO also caused release of vWF, the other principal protein associated with these organelles (15). Therefore, XO and endogenous NO appear to have opposing effects on the activation of Weibel-Palade bodies. This Yin-Yang relationship may also explain why the selectin antagonist fucoidan abolishes lung injury in L-NAME-treated rats subjected to intestinal ischemia-reperfusion (20), a condition that causes increased circulating levels of XO (17).

Suppression of endogenous NO also increases P-selectin expression in vivo (1), and this in part has been attributed to activation of mast cells with consequent release of histamine, a potent stimulus for P-selectin expression (21). For example, treatment of rats with L-NAME causes intestinal mast cell degranulation (8). The present study, in which mast cells are not present, suggests that NO can have a direct effect on EC, acting in an autocrine fashion to stabilize Weibel-Palade bodies and decrease P-selectin-mediated neutrophil tethering.

In summary, treatment of EC with XO initiates both pro- and antiadhesive pathways, the latter being mediated by endogenous NO. Such stimulation of NO production by oxidant-stressed endothelium may be an important protective response that diminishes indiscriminate dissemination of inflammation during systemic illnesses such as sepsis, shock, and multiorgan failure.

ACKNOWLEDGEMENTS

This work was supported by the American Heart Association and National Heart, Lung, and Blood Institute Grants R29-HL-52591, P50-HL-40784, and R01-HL-45582. B. M. Hybertson is a fellow of the Parker B. Francis Foundation, and L. S. Terada is an Established Investigator of the American Heart Association.

FOOTNOTES

Address for reprint requests: L. S. Terada, Webb-Waring Institute for Biomedical Research, Univ. of Colorado Health Sciences Center, Box C322, 4200 E. Ninth Ave., Denver, CO 80262.

Received 30 July 1996; accepted in final form 25 October 1996.

REFERENCES

1. Davenpeck, K. L., T. W. Gauthier, and A. M. Lefer. Inhibition of endothelial-derived nitric oxide promotes P-selectin expression and actions in the rat microcirculation. Gastroenterology 107: 1050-1058, 1994. [Medline]
2. Dreher, D., and A. F. Junod. Differential effects of superoxide, hydrogen peroxide, and hydroxyl radical on intracellular calcium in human endothelial cells. J. Cell. Physiol. 162: 147-153, 1995. [Medline]
3. Gaboury, J., R. C. Woodman, D. N. Granger, P. Reinhardt, and P. Kubes. Nitric oxide prevents leukocyte adherence: role of superoxide. Am. J. Physiol. 265 (Heart Circ. Physiol. 34): H862-H867, 1993. [Abstract/Free Full Text]
4. Gauthier, T. W., K. L. Davenpeck, and A. M. Lefer. Nitric oxide attenuates leukocyte-endothelial interaction via P-selectin in splanchnic ischemia-reperfusion. Am. J. Physiol. 267 (Gastrointest. Liver Physiol. 30): G562-G568, 1994. [Abstract/Free Full Text]
5. Gross, S. S., E. A. Jaffe, R. Levi, and R. G. Kilbourn. Cytokine-activated endothelial cells express an isotype of nitric oxide synthase which is tetrahydrobiopterin-dependent, calmodulin-independent and inhibited by arginine analogs with a rank-order of potency characteristic of activated macrophages. Biochem. Biophys. Res. Commun. 178: 823-829, 1991. [Medline]
6. Grum, C. M., R. A. Ragsdale, L. H. Ketai, and R. H. Simon. Plasma xanthine oxidase activity in patients with ARDS. J. Crit. Care 2: 22-26, 1987.
7. James, J. P., T. R. J. Stevens, N. D. Hall, P. J. Maddison, N. J. Goulding, A. Silman, S. Holligan, and C. Black. Factor VIII related antigen in connective tissue disease patients and relatives. Br. J. Rheum. 29: 6-9, 1990. [Abstract/Free Full Text]
8. Kubes, P., S. Kanwar, X. F. Niu, and J. P. Gaboury. Nitric oxide synthesis inhibition induces leukocyte adhesion via superoxide and mast cells. FASEB J. 7: 1293-1299, 1993. [Abstract]
9. Kubes, P., I. Kurose, and D. N. Granger. NO donors prevent integrin-induced leukocyte adhesion but not P-selectin-dependent rolling in postischemic venules. Am. J. Physiol. 267 (Heart Circ. Physiol. 36): H931-H937, 1994. [Abstract/Free Full Text]
10. Kubes, P., M. Suzuki, and D. N. Granger. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc. Natl. Acad. Sci. USA 88: 4651-4655, 1991. [Abstract/Free Full Text]
11. Kuchan, M. J., H. Jo, and J. A. Frangos. Role of G proteins in shear stress-mediated nitric oxide production by endothelial cells. Am. J. Physiol. 267 (Cell Physiol. 36): C753-C758, 1994. [Abstract/Free Full Text]
12. Kurose, I., P. Kubes, R. Wolf, D. C. Anderson, J. Paulson, M. Miyasaka, and D. N. Granger. Inhibition of nitric oxide production: mechanisms of vascular albumin leakage. Circ. Res. 73: 164-171, 1993. [Abstract]
13. Li, X., K. Abki, J. Rawn, C. R. Mackay, and S. J. Mentzer. LFA-1 and L-selectin regulation of recirculating lymphocyte tethering and rolling on lung microvascular endothelium. Am. J. Respir. Cell Mol. Biol. 14: 398-406, 1996. [Abstract]
14. Lipowsky, H. H., S. Kovalcheck, and B. W. Zweifach. The distribution of blood rheological parameters in the microvasculature of cat mesentery. Circ. Res. 43: 738-749, 1978. [Abstract/Free Full Text]
15. McEver, R. P., J. H. Beckstead, K. L. Moore, L. Marshall-Carlson, and D. F. Bainton. GMP-140, a platelet alpha-granule membrane protein, is also sythesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J. Clin. Invest. 84: 92-99, 1989.
16. Niu, X., C. W. Smith, and P. Kubes. Intracellular oxidative stress induced by nitric oxide synthesis inhibition increases endothelial cell adhesion to neutrophils. Circ. Res. 74: 1133-1140, 1994. [Abstract/Free Full Text]
17. Terada, L. S., J. J. Dormish, P. F. Shanley, J. A. Leff, B. O. Anderson, and J. E. Repine. Circulating xanthine oxidase increases following intestinal ischemia-reperfusion and mediates lung neutrophil sequestration. Am. J. Physiol. 263 (Lung Cell. Mol. Physiol. 7): L394-L401, 1992. [Abstract/Free Full Text]
18. Terada, L. S., D. M. Guidot, J. A. Leff, I. R. Willingham, M. E. Hanley, D. Piermattei, and J. E. Repine. Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity. Proc. Natl. Acad. Sci. USA 89: 3362-3366, 1992. [Abstract/Free Full Text]
19. Terada, L. S., B. M. Hybertson, K. G. Connelly, D. Weill, D. Piermattei, and J. E. Repine. Xanthine oxidase increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin mechanism. J. Appl. Physiol. 82: 865-872, 1997.
20. Terada, L. S., N. N. Mahr, and E. D. Jacobson. Nitric oxide decreases acute lung injury following intestinal ischemia. J. Appl. Physiol. 81: 2456-2460, 1996. [Abstract/Free Full Text]
21. Thorlacius, H., J. Raud, S. Rosengren-Beezley, M. J. Forrest, P. Hedqvist, and L. Lindbom. Mast cell activation induces P-selectin-dependent leukocyte rolling and adhesion in postcapillary venules in vivo. Biochem. Biophys. Res. Commun. 203: 1043-1049, 1994. [Medline]
22. Vischer, U. M., L. Jornot, C. B. Wollheim, and J. M. Theler. Reactive oxygen intermediates induce regulated secretion of von Willebrand factor from cultured human vascular endothelial cells. Blood 85: 3164-3172, 1995. [Abstract/Free Full Text]
23. Weinbroum, A., V. G. Nielsen, S. Tan, S. Gelman, S. Matalon, K. A. Skinner, E. Bradley, and D. A. Parks. Liver ischemia-reperfusion increases pulmonary permeability in rat: role of circulating xanthine oxidase. Am. J. Physiol. 268 (Gastrointest. Liver Physiol. 31): G988-G996, 1995. [Abstract/Free Full Text]
0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society



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