Abstract
Neutrophil adherence and/or aggregation has been implicated in ischemia reperfusion injuries. We examined the role of P-selectin in PMN-mediated injury after reperfusion of the rabbit ear. The ear was partially amputated, and then reattached leaving the central artery and vein intact. To induce ischemia the central artery was then occluded. Treatment was at reperfusion with either saline or one of two murine P-selectin mAbs, designated PB1.3 and PNB1.6 mAb PB1.3 cross-reacts with rabbit P-selectin and prevents histamine-induced leukocyte rolling, whereas PNB1.6 does not. Using a peroxidase-antiperoxidase system P-selectin was detected in the ischemic ear, but not in the nonischemic ear. Ear volume increased to 5.3 times baseline in the saline-treated animals (n = 8), 6.6 times baseline in the nonblocking mAb PNB1.6-treated animals (n = 2), and 3.7 times baseline in the blocking mAb PB1.3-treated animals (n = 8). Estimated tissue necrosis of the combined saline- and PNB1.6-treated animals was 46 vs. 2.7% for the mAb PB1.3-treated animals. We conclude that: (a) P-selectin is expressed in ischemia reperfusion; (b) P-selectin participates in PMN-endothelial cell interactions in ischemia reperfusion; and (c) inhibiting P-selectin adhesion significantly reduces reperfusion injury.
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Selected References
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- ALLISON F., Jr, SMITH M. R., WOOD W. B., Jr Studies on the pathogenesis of acute inflammation. I. The inflammatory reaction to thermal injury as observed in the rabbit ear chamber. J Exp Med. 1955 Dec 1;102(6):655–668. doi: 10.1084/jem.102.6.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arfors K. E., Lundberg C., Lindbom L., Lundberg K., Beatty P. G., Harlan J. M. A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood. 1987 Jan;69(1):338–340. [PubMed] [Google Scholar]
- Arnaout M. A. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood. 1990 Mar 1;75(5):1037–1050. [PubMed] [Google Scholar]
- Carlos T. M., Harlan J. M. Membrane proteins involved in phagocyte adherence to endothelium. Immunol Rev. 1990 Apr;114:5–28. doi: 10.1111/j.1600-065x.1990.tb00559.x. [DOI] [PubMed] [Google Scholar]
- Corral L., Singer M. S., Macher B. A., Rosen S. D. Requirement for sialic acid on neutrophils in a GMP-140 (PADGEM) mediated adhesive interaction with activated platelets. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1349–1356. doi: 10.1016/0006-291x(90)91598-m. [DOI] [PubMed] [Google Scholar]
- Etzioni A., Frydman M., Pollack S., Avidor I., Phillips M. L., Paulson J. C., Gershoni-Baruch R. Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med. 1992 Dec 17;327(25):1789–1792. doi: 10.1056/NEJM199212173272505. [DOI] [PubMed] [Google Scholar]
- Goldblum S. E., Wu K. M., Jay M. Lung myeloperoxidase as a measure of pulmonary leukostasis in rabbits. J Appl Physiol (1985) 1985 Dec;59(6):1978–1985. doi: 10.1152/jappl.1985.59.6.1978. [DOI] [PubMed] [Google Scholar]
- Granger D. N., Höllwarth M. E., Parks D. A. Ischemia-reperfusion injury: role of oxygen-derived free radicals. Acta Physiol Scand Suppl. 1986;548:47–63. [PubMed] [Google Scholar]
- Granger D. N. Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am J Physiol. 1988 Dec;255(6 Pt 2):H1269–H1275. doi: 10.1152/ajpheart.1988.255.6.H1269. [DOI] [PubMed] [Google Scholar]
- Gundel R. H., Wegner C. D., Torcellini C. A., Clarke C. C., Haynes N., Rothlein R., Smith C. W., Letts L. G. Endothelial leukocyte adhesion molecule-1 mediates antigen-induced acute airway inflammation and late-phase airway obstruction in monkeys. J Clin Invest. 1991 Oct;88(4):1407–1411. doi: 10.1172/JCI115447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hattori R., Hamilton K. K., Fugate R. D., McEver R. P., Sims P. J. Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J Biol Chem. 1989 May 15;264(14):7768–7771. [PubMed] [Google Scholar]
- Hattori R., Hamilton K. K., McEver R. P., Sims P. J. Complement proteins C5b-9 induce secretion of high molecular weight multimers of endothelial von Willebrand factor and translocation of granule membrane protein GMP-140 to the cell surface. J Biol Chem. 1989 May 25;264(15):9053–9060. [PubMed] [Google Scholar]
- Henson P. M., Zanolari B., Schwartzman N. A., Hong S. R. Intracellular control of human neutrophil secretion. I. C5a-induced stimulus-specific desensitization and the effects of cytochalasin B. J Immunol. 1978 Sep;121(3):851–855. [PubMed] [Google Scholar]
- Hernandez L. A., Grisham M. B., Twohig B., Arfors K. E., Harlan J. M., Granger D. N. Role of neutrophils in ischemia-reperfusion-induced microvascular injury. Am J Physiol. 1987 Sep;253(3 Pt 2):H699–H703. doi: 10.1152/ajpheart.1987.253.3.H699. [DOI] [PubMed] [Google Scholar]
- Horgan M. J., Wright S. D., Malik A. B. Antibody against leukocyte integrin (CD18) prevents reperfusion-induced lung vascular injury. Am J Physiol. 1990 Oct;259(4 Pt 1):L315–L319. doi: 10.1152/ajplung.1990.259.4.L315. [DOI] [PubMed] [Google Scholar]
- Kaslovsky R. A., Horgan M. J., Lum H., McCandless B. K., Gilboa N., Wright S. D., Malik A. B. Pulmonary edema induced by phagocytosing neutrophils. Protective effect of monoclonal antibody against phagocyte CD18 integrin. Circ Res. 1990 Oct;67(4):795–802. doi: 10.1161/01.res.67.4.795. [DOI] [PubMed] [Google Scholar]
- Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
- Ley K., Gaehtgens P., Fennie C., Singer M. S., Lasky L. A., Rosen S. D. Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo. Blood. 1991 Jun 15;77(12):2553–2555. [PubMed] [Google Scholar]
- McEver R. P., Beckstead J. H., Moore K. L., Marshall-Carlson L., Bainton D. F. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest. 1989 Jul;84(1):92–99. doi: 10.1172/JCI114175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McEver R. P. GMP-140: a receptor for neutrophils and monocytes on activated platelets and endothelium. J Cell Biochem. 1991 Feb;45(2):156–161. doi: 10.1002/jcb.240450206. [DOI] [PubMed] [Google Scholar]
- Mileski W. J., Winn R. K., Vedder N. B., Pohlman T. H., Harlan J. M., Rice C. L. Inhibition of CD18-dependent neutrophil adherence reduces organ injury after hemorrhagic shock in primates. Surgery. 1990 Aug;108(2):206–212. [PubMed] [Google Scholar]
- Moore K. L., Stults N. L., Diaz S., Smith D. F., Cummings R. D., Varki A., McEver R. P. Identification of a specific glycoprotein ligand for P-selectin (CD62) on myeloid cells. J Cell Biol. 1992 Jul;118(2):445–456. doi: 10.1083/jcb.118.2.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore K. L., Varki A., McEver R. P. GMP-140 binds to a glycoprotein receptor on human neutrophils: evidence for a lectin-like interaction. J Cell Biol. 1991 Feb;112(3):491–499. doi: 10.1083/jcb.112.3.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Mulligan M. S., Varani J., Dame M. K., Lane C. L., Smith C. W., Anderson D. C., Ward P. A. Role of endothelial-leukocyte adhesion molecule 1 (ELAM-1) in neutrophil-mediated lung injury in rats. J Clin Invest. 1991 Oct;88(4):1396–1406. doi: 10.1172/JCI115446. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parks D. A., Granger D. N. Contributions of ischemia and reperfusion to mucosal lesion formation. Am J Physiol. 1986 Jun;250(6 Pt 1):G749–G753. doi: 10.1152/ajpgi.1986.250.6.G749. [DOI] [PubMed] [Google Scholar]
- 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]
- Polley M. J., Phillips M. L., Wayner E., Nudelman E., Singhal A. K., Hakomori S., Paulson J. C. CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6224–6228. doi: 10.1073/pnas.88.14.6224. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schierwagen C., Bylund-Fellenius A. C., Lundberg C. Improved method for quantification of tissue PMN accumulation measured by myeloperoxidase activity. J Pharmacol Methods. 1990 May;23(3):179–186. doi: 10.1016/0160-5402(90)90061-o. [DOI] [PubMed] [Google Scholar]
- Simpson P. J., Todd R. F., 3rd, Fantone J. C., Mickelson J. K., Griffin J. D., Lucchesi B. R. Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest. 1988 Feb;81(2):624–629. doi: 10.1172/JCI113364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith S. M., Holm-Rutili L., Perry M. A., Grisham M. B., Arfors K. E., Granger D. N., Kvietys P. R. Role of neutrophils in hemorrhagic shock-induced gastric mucosal injury in the rat. Gastroenterology. 1987 Sep;93(3):466–471. doi: 10.1016/0016-5085(87)90907-3. [DOI] [PubMed] [Google Scholar]
- Thornton M. A., Winn R., Alpers C. E., Zager R. A. An evaluation of the neutrophil as a mediator of in vivo renal ischemic-reperfusion injury. Am J Pathol. 1989 Sep;135(3):509–515. [PMC free article] [PubMed] [Google Scholar]
- Vedder N. B., Fouty B. W., Winn R. K., Harlan J. M., Rice C. L. Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock. Surgery. 1989 Sep;106(3):509–516. [PubMed] [Google Scholar]
- Vedder N. B., Winn R. K., Rice C. L., Chi E. Y., Arfors K. E., Harlan J. M. A monoclonal antibody to the adherence-promoting leukocyte glycoprotein, CD18, reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits. J Clin Invest. 1988 Mar;81(3):939–944. doi: 10.1172/JCI113407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiss S. J., Young J., LoBuglio A. F., Slivka A., Nimeh N. F. Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells. J Clin Invest. 1981 Sep;68(3):714–721. doi: 10.1172/JCI110307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weller A., Isenmann S., Vestweber D. Cloning of the mouse endothelial selectins. Expression of both E- and P-selectin is inducible by tumor necrosis factor alpha. J Biol Chem. 1992 Jul 25;267(21):15176–15183. [PubMed] [Google Scholar]
- Weyrich A. S., Ma X. Y., Lefer D. J., Albertine K. H., Lefer A. M. In vivo neutralization of P-selectin protects feline heart and endothelium in myocardial ischemia and reperfusion injury. J Clin Invest. 1993 Jun;91(6):2620–2629. doi: 10.1172/JCI116501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhou Q., Moore K. L., Smith D. F., Varki A., McEver R. P., Cummings R. D. The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells. J Cell Biol. 1991 Oct;115(2):557–564. doi: 10.1083/jcb.115.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Andrian U. H., Chambers J. D., McEvoy L. M., Bargatze R. F., Arfors K. E., Butcher E. C. Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7538–7542. doi: 10.1073/pnas.88.17.7538. [DOI] [PMC free article] [PubMed] [Google Scholar]