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. 1995 Oct;96(4):2009–2016. doi: 10.1172/JCI118248

Impairment of selectin-mediated leukocyte adhesion to venular endothelium in spontaneously hypertensive rats.

M Suematsu 1, H Suzuki 1, T Tamatani 1, Y Iigou 1, F A DeLano 1, M Miyasaka 1, M J Forrest 1, R Kannagi 1, B W Zweifach 1, Y Ishimura 1, et al.
PMCID: PMC185839  PMID: 7560094

Abstract

The present study was designed to elucidate whether molecular mechanisms for leukocyte adhesion to microvascular endothelium may differ between spontaneously hypertensive rats and Wistar Kyoto rats. Leukocyte rolling and adhesion were investigated while monitoring venular wall shear rates in the mesenteric microcirculation stimulated with histamine or tert-butyl hydroperoxide in the two strains. In Wistar Kyoto rats, 10 microM histamine as well as 500 microM tertbutyl hydroperoxide promoted a significant reduction of venular leukocyte rolling velocity and subsequent adhesion. These changes in leukocyte behavior were blocked by monoclonal antibodies against P-selectin (PB 1.3) and against sialyl Lewis X-like carbohydrates (2H5). However, spontaneously hypertensive rats exhibited a blunted response of the stimulus-elicited leukocyte rolling, which was associated with impairment of venular P-selectin expression as well as a decrease in the expression of sialyl Lewis X-like carbohydrates on circulating neutrophils. No significant differences were detected between the two strains not only in the surface CD11b/CD18 expression but also in the CD18-mediated adhesivity of neutrophils to intracellular adhesion molecule-1 transfectants in vitro. These results suggest that impairment of selectin-mediated leukocyte adhesion is an event responsible for disorders of inflammatory responses in spontaneously hypertensive rats.

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  1. Arndt H., Smith C. W., Granger D. N. Leukocyte-endothelial cell adhesion in spontaneously hypertensive and normotensive rats. Hypertension. 1993 May;21(5):667–673. doi: 10.1161/01.hyp.21.5.667. [DOI] [PubMed] [Google Scholar]
  2. Asako H., Kurose I., Wolf R., DeFrees S., Zheng Z. L., Phillips M. L., Paulson J. C., Granger D. N. Role of H1 receptors and P-selectin in histamine-induced leukocyte rolling and adhesion in postcapillary venules. J Clin Invest. 1994 Apr;93(4):1508–1515. doi: 10.1172/JCI117129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barroso-Aranda J., Schmid-Schönbein G. W. Transformation of neutrophils as indicator of irreversibility in hemorrhagic shock. Am J Physiol. 1989 Sep;257(3 Pt 2):H846–H852. doi: 10.1152/ajpheart.1989.257.3.H846. [DOI] [PubMed] [Google Scholar]
  4. Bienvenu K., Granger D. N. Molecular determinants of shear rate-dependent leukocyte adhesion in postcapillary venules. Am J Physiol. 1993 May;264(5 Pt 2):H1504–H1508. doi: 10.1152/ajpheart.1993.264.5.H1504. [DOI] [PubMed] [Google Scholar]
  5. Davis M. J. Determination of volumetric flow in capillary tubes using an optical Doppler velocimeter. Microvasc Res. 1987 Sep;34(2):223–230. doi: 10.1016/0026-2862(87)90055-0. [DOI] [PubMed] [Google Scholar]
  6. House S. D., Lipowsky H. H. Leukocyte-endothelium adhesion: microhemodynamics in mesentery of the cat. Microvasc Res. 1987 Nov;34(3):363–379. doi: 10.1016/0026-2862(87)90068-9. [DOI] [PubMed] [Google Scholar]
  7. Kita Y., Takashi T., Iigo Y., Tamatani T., Miyasaka M., Horiuchi T. Sequence and expression of rat ICAM-1. Biochim Biophys Acta. 1992 May 7;1131(1):108–110. doi: 10.1016/0167-4781(92)90107-b. [DOI] [PubMed] [Google Scholar]
  8. Kubes P., Kanwar S. Histamine induces leukocyte rolling in post-capillary venules. A P-selectin-mediated event. J Immunol. 1994 Apr 1;152(7):3570–3577. [PubMed] [Google Scholar]
  9. Lorant D. E., Topham M. K., Whatley R. E., McEver R. P., McIntyre T. M., Prescott S. M., Zimmerman G. A. Inflammatory roles of P-selectin. J Clin Invest. 1993 Aug;92(2):559–570. doi: 10.1172/JCI116623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mayadas T. N., Johnson R. C., Rayburn H., Hynes R. O., Wagner D. D. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell. 1993 Aug 13;74(3):541–554. doi: 10.1016/0092-8674(93)80055-j. [DOI] [PubMed] [Google Scholar]
  11. Mulligan M. S., Polley M. J., Bayer R. J., Nunn M. F., Paulson J. C., Ward P. A. Neutrophil-dependent acute lung injury. Requirement for P-selectin (GMP-140). J Clin Invest. 1992 Oct;90(4):1600–1607. doi: 10.1172/JCI116029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nakazono K., Watanabe N., Matsuno K., Sasaki J., Sato T., Inoue M. Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10045–10048. doi: 10.1073/pnas.88.22.10045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Patel K. D., Zimmerman G. A., Prescott S. M., McEver R. P., McIntyre T. M. Oxygen radicals induce human endothelial cells to express GMP-140 and bind neutrophils. J Cell Biol. 1991 Feb;112(4):749–759. doi: 10.1083/jcb.112.4.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sawada M., Takada A., Ohwaki I., Takahashi N., Tateno H., Sakamoto J., Kannagi R. Specific expression of a complex sialyl Lewis X antigen on high endothelial venules of human lymph nodes: possible candidate for L-selectin ligand. Biochem Biophys Res Commun. 1993 May 28;193(1):337–347. doi: 10.1006/bbrc.1993.1629. [DOI] [PubMed] [Google Scholar]
  15. Schmid-Schönbein G. W., Seiffge D., DeLano F. A., Shen K., Zweifach B. W. Leukocyte counts and activation in spontaneously hypertensive and normotensive rats. Hypertension. 1991 Mar;17(3):323–330. doi: 10.1161/01.hyp.17.3.323. [DOI] [PubMed] [Google Scholar]
  16. Schmid-Schönbein G. W., Skalak R., Simon S. I., Engler R. L. The interaction between leukocytes and endothelium in vivo. Ann N Y Acad Sci. 1987;516:348–361. doi: 10.1111/j.1749-6632.1987.tb33055.x. [DOI] [PubMed] [Google Scholar]
  17. Schmid-Schönbein G. W., Zweifach B. W., DeLano F. A., Chen P. C. Microvascular tone in a skeletal muscle of spontaneously hypertensive rats. Hypertension. 1987 Feb;9(2):164–171. doi: 10.1161/01.hyp.9.2.164. [DOI] [PubMed] [Google Scholar]
  18. Shen K., DeLano F. A., Zweifach B. W., Schmid-Schönbein G. W. Circulating leukocyte counts, activation, and degranulation in Dahl hypertensive rats. Circ Res. 1995 Feb;76(2):276–283. doi: 10.1161/01.res.76.2.276. [DOI] [PubMed] [Google Scholar]
  19. Shichijo K., Ito M., Sekine I. The mechanism of low susceptibility to stress in gastric lesions of spontaneously hypertensive rats. Life Sci. 1991;49(26):2023–2029. doi: 10.1016/0024-3205(91)90645-r. [DOI] [PubMed] [Google Scholar]
  20. Shikuwa S., Naito S., Chaotien H., Shichijo K., Kawase Y., Ito M., Sekine I., Imamura K. The role of the sympathetic nervous system in cysteamine-induced gastric lesions in rats. Scand J Gastroenterol Suppl. 1989;162:206–209. doi: 10.3109/00365528909091162. [DOI] [PubMed] [Google Scholar]
  21. Suematsu M., Kurose I., Asako H., Miura S., Tsuchiya M. In vivo visualization of oxyradical-dependent photoemission during endothelium-granulocyte interaction in microvascular beds treated with platelet-activating factor. J Biochem. 1989 Aug;106(2):355–360. doi: 10.1093/oxfordjournals.jbchem.a122857. [DOI] [PubMed] [Google Scholar]
  22. Suematsu M., Schmid-Schönbein G. W., Chavez-Chavez R. H., Yee T. T., Tamatani T., Miyasaka M., Delano F. A., Zweifach B. W. In vivo visualization of oxidative changes in microvessels during neutrophil activation. Am J Physiol. 1993 Mar;264(3 Pt 2):H881–H891. doi: 10.1152/ajpheart.1993.264.3.H881. [DOI] [PubMed] [Google Scholar]
  23. Suematsu M., Tamatani T., Delano F. A., Miyasaka M., Forrest M., Suzuki H., Schmid-Schönbein G. W. Microvascular oxidative stress preceding leukocyte activation elicited by in vivo nitric oxide suppression. Am J Physiol. 1994 Jun;266(6 Pt 2):H2410–H2415. doi: 10.1152/ajpheart.1994.266.6.H2410. [DOI] [PubMed] [Google Scholar]
  24. Suzuki H., Schmid-Schönbein G. W., Suematsu M., DeLano F. A., Forrest M. J., Miyasaka M., Zweifach B. W. Impaired leukocyte-endothelial cell interaction in spontaneously hypertensive rats. Hypertension. 1994 Dec;24(6):719–727. doi: 10.1161/01.hyp.24.6.719. [DOI] [PubMed] [Google Scholar]
  25. Suzuki H., Suematsu M., Miura S., Liu Y. Y., Watanabe K., Miyasaka M., Tsurufuji S., Tsuchiya M. Rat CINC/gro: a novel mediator for locomotive and secretagogue activation of neutrophils in vivo. J Leukoc Biol. 1994 May;55(5):652–657. doi: 10.1002/jlb.55.5.652. [DOI] [PubMed] [Google Scholar]
  26. Suzuki H., Swei A., Zweifach B. W., Schmid-Schönbein G. W. In vivo evidence for microvascular oxidative stress in spontaneously hypertensive rats. Hydroethidine microfluorography. Hypertension. 1995 May;25(5):1083–1089. doi: 10.1161/01.hyp.25.5.1083. [DOI] [PubMed] [Google Scholar]
  27. Suzuki H., Zweifach B. W., Forrest M. J., Schmid-Schönbein G. W. Modification of leukocyte adhesion in spontaneously hypertensive rats by adrenal corticosteroids. J Leukoc Biol. 1995 Jan;57(1):20–26. [PubMed] [Google Scholar]
  28. Tamatani T., Kitamura F., Kuida K., Shirao M., Mochizuki M., Suematsu M., Schmid-Schönbein G. W., Watanabe K., Tsurufuji S., Miyasaka M. Characterization of rat LECAM-1 (L-selectin) by the use of monoclonal antibodies and evidence for the presence of soluble LECAM-1 in rat sera. Eur J Immunol. 1993 Sep;23(9):2181–2188. doi: 10.1002/eji.1830230920. [DOI] [PubMed] [Google Scholar]
  29. Tamatani T., Kotani M., Tanaka T., Miyasaka M. Molecular mechanisms underlying lymphocyte recirculation. II. Differential regulation of LFA-1 in the interaction between lymphocytes and high endothelial cells. Eur J Immunol. 1991 Mar;21(3):855–858. doi: 10.1002/eji.1830210351. [DOI] [PubMed] [Google Scholar]
  30. Watanabe K., Suematsu M., Iida M., Takaishi K., Iizuka Y., Suzuki H., Suzuki M., Tsuchiya M., Tsurufuji S. Effect of rat CINC/gro, a member of the interleukin-8 family, on leukocytes in microcirculation of the rat mesentery. Exp Mol Pathol. 1992 Feb;56(1):60–69. doi: 10.1016/0014-4800(92)90023-5. [DOI] [PubMed] [Google Scholar]
  31. Wennberg E., Hagberg H., Haljamäe H. The response of the awake spontaneously hypertensive rat (SHR) to acute blood loss. Acta Anaesthesiol Scand. 1984 Aug;28(4):457–461. doi: 10.1111/j.1399-6576.1984.tb02098.x. [DOI] [PubMed] [Google Scholar]
  32. Williams J. H., Jr, Moser K. M., Ulich T., Cairo M. S. Harvesting the noncirculating pool of polymorphonuclear leukocytes in rats by hetastarch exchange transfusion (HET): yield and functional assessment. J Leukoc Biol. 1987 Nov;42(5):455–462. doi: 10.1002/jlb.42.5.455. [DOI] [PubMed] [Google Scholar]
  33. Winn R. K., Liggitt D., Vedder N. B., Paulson J. C., Harlan J. M. Anti-P-selectin monoclonal antibody attenuates reperfusion injury to the rabbit ear. J Clin Invest. 1993 Oct;92(4):2042–2047. doi: 10.1172/JCI116799. [DOI] [PMC free article] [PubMed] [Google Scholar]

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