Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to endothelium in vivo.
Open accessAbstract
A common feature of cigarette-smoke (CS)-associated diseases such as atherosclerosis and pulmonary emphysema is the activation, aggregation, and adhesion of leukocytes to micro- and macrovascular endothelium. A previous study, using a skinfold chamber model for intravital fluorescence microscopy in awake hamsters, has shown that exposure of hamsters to the smoke generated by one research cigarette elicits the adhesion of fluorescently labeled leukocytes to the endothelium of arterioles and small venules. By the combined use of intravital microscopy and scanning electron microscopy, we now demonstrate in the same animal model that (i) CS-induced leukocyte adhesion is not confined to the microcirculation, but that leukocytes also adhere singly and in clusters to the aortic endothelium; (ii) CS induces the formation in the bloodstream of aggregates between leukocytes and platelets; and (iii) CS-induced leukocyte adhesion to micro- and macrovascular endothelium and leukocyte-platelet aggregate formation are almost entirely prevented by dietary or intravenous pretreatment with the water-soluble antioxidant vitamin C (venules, 21.4 +/- 11.0 vs. 149.6 +/- 38.7 leukocytes per mm2, P < 0.01; arterioles, 8.5 +/- 4.2 vs. 54.3 +/- 21.6 leukocytes per mm2, P < 0.01; aortas, 0.8 +/- 0.4 vs. 12.4 +/- 5.6 leukocytes per mm2, P < 0.01; means +/- SD of n = 7 animals, 15 min after CS exposure). No inhibitory effect was observed by pretreatment of the animals with the lipid-soluble antioxidants vitamin E or probucol. The protective effects of vitamin C on CS-induced leukocyte adhesion and aggregation were seen at vitamin C plasma levels (55.6 +/- 22.2 microM, n = 7) that can easily be reached in humans by dietary means or supplementation, suggesting that vitamin C effectively contributes to protection from CS-associated cardiovascular and pulmonary diseases in humans.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Cites
Tissue Destruction by Neutrophils
Epstein, F. H., & Weiss, S. J. (1989) · New England Journal of Medicine · doi:10.1056/nejm198902093200606 · Cited by 3,950 · see citing works
Vitamin E Consumption and the Risk of Coronary Heart Disease in Men
Rimm, E. B., Stampfer, M. J., Ascherio, A., Giovannucci, E. L., Colditz, G. A., & Willett, W. C. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282004 · Cited by 2,335 · see citing works
Ascorbate is an outstanding antioxidant in human blood plasma
Frei, B., England, L., & Ames, B. N. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.16.6377 · Cited by 1,870 · see citing works
Self-citationFree-Radical Chemistry of Cigarette Smoke and Its Toxicological Implications
CHURCH, D. F., & PRYOR, W. A. (1985) · Environmental Health Perspectives · doi:10.1289/ehp.8564111 · Cited by 1,442 · see citing works
Antioxidant defenses and lipid peroxidation in human blood plasma.
Frei, B. B., Stocker, R., & Ames, B. N. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.24.9748 · Cited by 1,254 · see citing works
Self-citationOxidative Stress: Oxidants and Antioxidants.
Haddock, P. (1992) · Cardiovascular Research · doi:10.1093/cvr/26.8.816a · Cited by 1,187 · see citing works
Carew, T. E., Schwenke, D. C., & Steinberg, D. H. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.21.7725 · Cited by 1,040 · see citing works
Pharmacologic Aspects of Cigarette Smoking and Nicotine Addiction
Oates, J. A., Wood, A. J. J., & Benowitz, N. L. (1988) · New England Journal of Medicine · doi:10.1056/nejm198811173192005 · Cited by 963 · see citing works
Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene
Riemersma, R. A., Wood, D. A., Oliver, M. F., Elton, R. A., Macintyre, C. C. A., & GEY, K. F. (1991) · The Lancet · doi:10.1016/0140-6736(91)93327-6 · Cited by 771 · see citing works
Role of vitamin E in preventing the oxidation of low-density lipoprotein
Esterbauer, H., Dieber‐Rotheneder, M., Striegl, G., & Waeg, G. (1991) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/53.1.314s · Cited by 640 · see citing works
Oxygen radicals induce human endothelial cells to express GMP-140 and bind neutrophils.
Patel, K. D., Zimmerman, G. A., Prescott, S. M., McEver, R. P., & McIntyre, T. M. (1991) · The Journal of Cell Biology · doi:10.1083/jcb.112.4.749 · Cited by 597 · see citing works
Vitamin C Intake and Mortality among a Sample of the United States Population
Enstrom, J., Kanim, L., & Klein, M. A. (1992) · Epidemiology · doi:10.1097/00001648-199205000-00003 · Cited by 580 · see citing works
Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis.
Janoff, A. (1985) · PubMed · doi:10.1164/arrd.1985.132.2.417 · Cited by 502 · see citing works
Frei, B. B., Forte, T. M., Ames, B. N., & Cross, C. E. (1991) · Biochemical Journal · doi:10.1042/bj2770133 · Cited by 471 · see citing works
Self-citationPRYOR, W. A., Prier, D. G., & CHURCH, D. F. (1983) · Environmental Health Perspectives · doi:10.1289/ehp.8347345 · Cited by 387 · see citing works
Rous-Whipple Award Lecture. Atherosclerosis: a defense mechanism gone awry.
Ross, R. (1993) · PubMed Central · Cited by 345 · see citing works
The influence of smoking on vitamin C status in adults.
Schectman, G., Byrd, J. C., & Gruchow, H. W. (1989) · American Journal of Public Health · doi:10.2105/ajph.79.2.158 · Cited by 343 · see citing works
GEY, K. F., Moser, U., Jordan, P., Stähelin, H., Eichholzer, M., & Lüdin, E. (1993) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/57.5.787s · Cited by 305 · see citing works
The Effect of Cigarette Smoking on Neutrophil Kinetics in Human Lungs
MacNee, W., Wiggs, B., Belzberg, A. S., & Hogg, J. C. (1989) · New England Journal of Medicine · doi:10.1056/nejm198910053211402 · Cited by 283 · see citing works
Smiley, P. L., Stremler, K. E., Prescott, S. M., Zimmerman, G., & McIntyre, T. M. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99133-7 · Cited by 218 · see citing works
GMP‐140: A receptor for neutrophils and monocytes on activated platelets and endothelium
McEver, R. P. (1991) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240450206 · Cited by 207 · see citing works
Halliwell, B., Wasil, M., & Grootveld, M. (1987) · FEBS Letters · doi:10.1016/0014-5793(87)81456-4 · Cited by 189 · see citing works
Dietary vitamin E and the attenuation of early lesion development in modified Watanabe rabbits
Williams, R. J., Motteram, J. M., Sharp, C. H., & Gallagher, P. J. (1992) · Atherosclerosis · doi:10.1016/0021-9150(92)90240-h · Cited by 165 · see citing works
Pittilo, R. M., Mackie, I. J., Rowles, P. M., et al. (1982) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1657250 · Cited by 121 · see citing works
Cigarette smoke elicits leukocyte adhesion to endothelium in hamsters: Inhibition by CuZn-SOD
Lehr, H., Kress, E., Menger, M. D., Friedl, H. P., Hübner, C., Arfors, K. E., & Meßmer, K. (1993) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(93)90138-k · Cited by 115 · see citing works
Self-citationEffect of probucol on the physical properties of low-density lipoproteins oxidized by copper
McLean, L. R., & Hagaman, K. A. (1989) · Biochemistry · doi:10.1021/bi00427a043 · Cited by 89 · see citing works
Kilburn, K. H., & McKenzie, W. N. (1975) · Science · doi:10.1126/science.1162344 · Cited by 87 · see citing works
Lehr, H., Hübner, C., Finckh, B., Angermüller, S., Nölte, D., Beisiegel†, U., Kohlschütter, A., & Meßmer, K. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115309 · Cited by 79 · see citing works
Self-citationCigarette smoking causes accumulation of polymorphonuclear leukocytes in alveolar septum.
Ludwig, P., Schwartz, B. A., Hoidal, J. R., et al. (1985) · PubMed · doi:10.1164/arrd.1985.131.6.828 · Cited by 72 · see citing works
Imaizumi, T., Satoh, K., Yoshida, H., et al. (1991) · Atherosclerosis · doi:10.1016/0021-9150(91)90231-q · Cited by 59 · see citing works
Activation of Neutrophils within Pulmonary Microvessels of Rabbits Exposed to Cigarette Smoke
Klut, M. E., Doerschuk, C. M., van Eeden, S. F., et al. (1993) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb/9.1.82 · Cited by 56 · see citing works
Anderson, R. (1991) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/53.1.358s · Cited by 55 · see citing works
Pryor, W. A., Dooley, M. M., & Church, D. F. (1986) · Chemico-Biological Interactions · doi:10.1016/0009-2797(86)90002-5 · Cited by 55 · see citing works
Nicotine and cigarette smoking: effects on the ultrastructure of aortic endothelium.
Pittilo, R. M., Bull, H. A., Gulati, S., et al. (1990) · PubMed · Cited by 48 · see citing works
Decreased Leukocyte Deformability after Acute Cigarette Smoking in Humans
Drost, E., Selby, C., Bridgeman, M. M. E., et al. (1993) · American Review of Respiratory Disease · doi:10.1164/ajrccm/148.5.1277 · Cited by 47 · see citing works
Mechanisms of tissue damage by leukocytes.
Lehr, H., & Arfors, K. E. (1994) · PubMed · Cited by 42 · see citing works
Self-citationNeutrophil kinetics during active cigarette smoking in rabbits
Bosken, C. H., Doerschuk, C. M., English, D. R., et al. (1991) · Journal of Applied Physiology · doi:10.1152/jappl.1991.71.2.630 · Cited by 38 · see citing works
Protective Effect of Vitamin E on Immune Triggered, Granulocyte Mediated Endothelial Injury
Boogaerts, M. A., Broeck, J. V., Deckmyn, H., et al. (1984) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1661027 · Cited by 33 · see citing works
In vitro effect of ascorbic acid on neutrophil–endothelial cell interaction
Jonas, E., Dwenger, A., & Hager, A. (1993) · Journal of Bioluminescence and Chemiluminescence · doi:10.1002/bio.1170080104 · Cited by 27 · see citing works
Frank, E. (1993) · PubMed · Cited by 21 · see citing works
Niewoehner, D. E., Peterson, F. J., & Hoidal, J. R. (1983) · PubMed · doi:10.1164/arrd.1983.127.2.227 · Cited by 5 · see citing works
Failure of High-Dose Vitamin E to Correct Ceruloplasmin Ferroxidase Deficiency in Cigarette Smokers
Pacht, E. R., & Davis, W. B. (1990) · American Review of Respiratory Disease · doi:10.1164/ajrccm/142.5.1063 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638 · see citing works
Vitamin effects on the immune system: Vitamins A and D take centre stage
Mora, J. R., Iwata, M., & von Andrian, U. H. (2008) · Nature Reviews Immunology · doi:10.1038/nri2378 · Cited by 1,559 · see citing works
Carr, A. C., & Frei, B. (1999) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.6.1086 · Cited by 940 · see citing works
Self-citationVitamin C in Human Health and Disease Is Still a Mystery? An Overview
Naidu, K. A. (2003) · Nutrition Journal · doi:10.1186/1475-2891-2-7 · Cited by 810 · see citing works
Antioxidant Vitamin C Improves Endothelial Dysfunction in Chronic Smokers
Heitzer, T., Just, H., & Mu¨nzel, T. (1996) · Circulation · doi:10.1161/01.cir.94.1.6 · Cited by 554 · see citing works
Weber, C., Erl, W., Weber, K., & Weber, P. C. (1996) · Circulation · doi:10.1161/01.cir.93.8.1488 · Cited by 195 · see citing works
Dietary supplement with vitamin C prevents nitrate tolerance
Bassenge, E., Fink, N., Skatchkov, M., & Fink, B. (1998) · Journal of Clinical Investigation · doi:10.1172/jci977 · Cited by 138 · see citing works
Tousoulis, D. (2003) · Atherosclerosis · doi:10.1016/s0021-9150(03)00250-8 · Cited by 60 · see citing works
Plasma-Saturating intakes of vitamin C confer maximal antioxidant protection to plasma
Johnston, C. S., & Cox, S. K. (2001) · Journal of the American College of Nutrition · doi:10.1080/07315724.2001.10719159 · Cited by 31 · see citing works
Scott, D. A., Poston, R. N., Wilson, R. F., Coward, P. Y., & Palmer, R. M. (2005) · Inflammation Research · doi:10.1007/s00011-004-1335-4 · Cited by 22 · see citing works
- Authors
- Lehr, H. A., Frei, B., & Arfors, K. E.
- Affiliations
- Institut für Chirurgische Forschung (DE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-08-02
- Volume
- 91
- Issue
- 16
- Pages
- 7688-7692
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44467
- OpenAlex
- W2052075519
- Cited by
- 167
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 1 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 7 · 2013: 3 · 2012: 3
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r29hl049954-05)
- National Heart, Lung, and Blood Institute (HL49954)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- vitamin C, cigarette smoke, leukocyte adhesion, leukocyte aggregation, platelet aggregation, endothelium, atherosclerosis, emphysema, antioxidants, vitamin E, probucol, intravital microscopy, hamster model, cardiovascular disease, lung disease
- MeSH terms
- Animals, Aorta, Ascorbic Acid, Cell Adhesion, Cell Aggregation, Endothelium, Vascular, Cricetinae, Leukocytes, Mesocricetus, Microcirculation, Microscopy, Electron, Scanning, Microscopy, Fluorescence, Probucol, Staining and Labeling, Superoxides, Vitamin E, Smoke Inhalation Injury, Reactive Oxygen Species
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review