Prevention of vasospasm by anti-CD11/CD18 monoclonal antibody therapy following subarachnoid hemorrhage in rabbits

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Object. Adhesion of leukocytes and their migration into the periadventitial space may be critical in the pathophysiology of vasospasm following subarachnoid hemorrhage (SAH). The cell adhesion molecules involved in this process are lymphocyte function—associated antigen—1 (CD11a/CD18) and macrophage antigen—1 (CD11b/CD18), which are present on neutrophils/macrophages, and intercellular adhesion molecule—1 (CD54), which is present in endothelial cells. A humanized monoclonal antibody (mAb), Hu23F2G, targets CD11/CD18 and prevents leukocyte adhesion to endothelial cells. In this study, systemic administration of Hu23F2G prevented vasospasm in the rabbit model of SAH.

Methods. Twenty-six New Zealand White rabbits were injected with autologous blood into the cisterna magna to induce SAH, after which they were randomized to receive injections of either Hu23F2G (10 animals) or a placebo at 30 minutes and 24 and 48 hours after SAH (six animals). Control animals underwent sham operations (four animals) or SAH alone (six animals). The animals were killed 72 hours after SAH, their bodies perfused and fixed, and their basilar arteries processed for morphometric analysis. Peripheral white blood cells (WBCs) were counted at 72 hours. The percentages of lumen patency were compared using the Student t-test. The presence of neutrophils and macrophages was confirmed by immunohistochemical analysis in which a rat anti—rabbit anti-CD18 mAb and cresyl violet were used.

Treatment with Hu23F2G resulted in the significant prevention of vasospasm. Animals treated with Hu23F2G had 90 ± 7% lumen patency compared with 65 ± 7% in the placebo group (p = 0.025). The percentage of lumen patency in the SAH-only group was 59 ± 10%. The mean WBC count was 16,300 ± 2710/µl in the treatment group, compared with 7000 ± 386/µl in the control group (p = 0.02). Administration of Hu23F2G produced increased numbers of WBCs in 70% of the animals treated.

Conclusions. This study supports the concept that leukocyte—endothelial cell interactions play an important role in the pathophysiology of chronic vasospasm after SAH. Systemic therapy with an anti-CD11/CD18 mAb prevents vasospasm after SAH by inhibiting adhesion of neutrophils and macrophages and their migration into the periadventitial space.

Article Information

Contributor Notes

Address reprint requests to: Rafael J. Tamargo, M.D., Department of Neurosurgery, The Johns Hopkins University School of Medicine, Meyer Building 8–181, 600 North Wolfe Street, Baltimore, Maryland 21287. email: rtamarg@jhmi.edu.
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References
  • 1.

    Aihara YKasuya HOnda Het al: Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage. Stroke 32:2122172001Aihara Y Kasuya H Onda H et al: Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage. Stroke 32:212–217 2001

    • Search Google Scholar
    • Export Citation
  • 2.

    Akopov SEGrigorian MRGabrielian ES: The endothelium-dependent relaxation of human middle cerebral artery: effects of activated neutrophils. Experientia 48:34361992Akopov SE Grigorian MR Gabrielian ES: The endothelium-dependent relaxation of human middle cerebral artery: effects of activated neutrophils. Experientia 48:34–36 1992

    • Search Google Scholar
    • Export Citation
  • 3.

    Anonymous: Hu23F2G. 23F2G, LeukArrest. Drugs R D 1:25261999Anonymous: Hu23F2G. 23F2G LeukArrest. Drugs R D 1:25–26 1999

  • 4.

    Bavbek MPolin RKwan ALet al: Monoclonal antibodies against ICAM-1 and CD18 attenuate cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. Stroke 29:193019361998Bavbek M Polin R Kwan AL et al: Monoclonal antibodies against ICAM-1 and CD18 attenuate cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. Stroke 29:1930–1936 1998

    • Search Google Scholar
    • Export Citation
  • 5.

    Becker KJ: Anti-leukocyte antibodies: LeukArrest (Hu23F2G) and Enlimomab (R6.5) in acute stroke. Curr Med Res Opin 18 (Suppl 2):S18S222002Becker KJ: Anti-leukocyte antibodies: LeukArrest (Hu23F2G) and Enlimomab (R6.5) in acute stroke. Curr Med Res Opin 18 (Suppl 2):S18–S22 2002

    • Search Google Scholar
    • Export Citation
  • 6.

    Berger MShankar VVafai A: Therapeutic applications of monoclonal antibodies. Am J Med Sci 324:14302002Berger M Shankar V Vafai A: Therapeutic applications of monoclonal antibodies. Am J Med Sci 324:14–30 2002

    • Search Google Scholar
    • Export Citation
  • 7.

    Bertsch TKuehl SMuehlhauser Fet al: Source of endothelin-1 in subarachnoid hemorrhage. Clin Chem Lab Med 39:3413452001Bertsch T Kuehl S Muehlhauser F et al: Source of endothelin-1 in subarachnoid hemorrhage. Clin Chem Lab Med 39:341–345 2001

    • Search Google Scholar
    • Export Citation
  • 8.

    Bowen JDPetersdorf SHRichards TLet al: Phase I study of a humanized anti-CD11/CD18 monoclonal antibody in multiple sclerosis. Clin Pharmacol Ther 64:3393461998Bowen JD Petersdorf SH Richards TL et al: Phase I study of a humanized anti-CD11/CD18 monoclonal antibody in multiple sclerosis. Clin Pharmacol Ther 64:339–346 1998

    • Search Google Scholar
    • Export Citation
  • 9.

    Champe MMcIntyre BWBerman PW: Monoclonal antibodies that block the activity of leukocyte function-associated antigen 1 recognize three discrete epitopes in the inserted domain of CD11a. J Biol Chem 270:138813941995Champe M McIntyre BW Berman PW: Monoclonal antibodies that block the activity of leukocyte function-associated antigen 1 recognize three discrete epitopes in the inserted domain of CD11a. J Biol Chem 270:1388–1394 1995

    • Search Google Scholar
    • Export Citation
  • 10.

    Chan RCDurity FAThompson GBet al: The role of the prostacyclin-thromboxane system in cerebral vasospasm following induced subarachnoid hemorrhage in the rabbit. J Neurosurg 61:112011281984Chan RC Durity FA Thompson GB et al: The role of the prostacyclin-thromboxane system in cerebral vasospasm following induced subarachnoid hemorrhage in the rabbit. J Neurosurg 61:1120–1128 1984

    • Search Google Scholar
    • Export Citation
  • 11.

    Chow MDumont ASKassell NF: Endothelin receptor antagonists and cerebral vasospasm: an update. Neurosurgery 51:133313422002Chow M Dumont AS Kassell NF: Endothelin receptor antagonists and cerebral vasospasm: an update. Neurosurgery 51:1333–1342 2002

    • Search Google Scholar
    • Export Citation
  • 12.

    Chyatte D: Prevention of chronic cerebral vasospasm in dogs with ibuprofen and high-dose methylprednisolone. Stroke 20:102110261989Chyatte D: Prevention of chronic cerebral vasospasm in dogs with ibuprofen and high-dose methylprednisolone. Stroke 20:1021–1026 1989

    • Search Google Scholar
    • Export Citation
  • 13.

    Chyatte DRusch NSundt TM Jr: Prevention of chronic experimental cerebral vasospasm with ibuprofen and high-dose methylprednisolone. J Neurosurg 59:9259321983Chyatte D Rusch N Sundt TM Jr: Prevention of chronic experimental cerebral vasospasm with ibuprofen and high-dose methylprednisolone. J Neurosurg 59:925–932 1983

    • Search Google Scholar
    • Export Citation
  • 14.

    Clatterbuck REGailloud POgata Let al: Prevention of cerebral vasospasm by a humanized anti-CD11/CD18 monoclonal antibody administered after experimental subarachnoid hemorrhage in nonhuman primates. J Neurosurg 99:3763822003Clatterbuck RE Gailloud P Ogata L et al: Prevention of cerebral vasospasm by a humanized anti-CD11/CD18 monoclonal antibody administered after experimental subarachnoid hemorrhage in nonhuman primates. J Neurosurg 99:376–382 2003

    • Search Google Scholar
    • Export Citation
  • 15.

    Clatterbuck REOshiro EMHoffman PAet al: Inhibition of vasospasm with lymphocyte function-associated antigen-1 monoclonal antibody in a femoral artery model in rats. J Neurosurg 97:6766822002Clatterbuck RE Oshiro EM Hoffman PA et al: Inhibition of vasospasm with lymphocyte function-associated antigen-1 monoclonal antibody in a femoral artery model in rats. J Neurosurg 97:676–682 2002

    • Search Google Scholar
    • Export Citation
  • 16.

    Diamond MSStaunton DEMarlin SDet al: Binding of the integrin Mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation. Cell 65:9619711991Diamond MS Staunton DE Marlin SD et al: Binding of the integrin Mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation. Cell 65:961–971 1991

    • Search Google Scholar
    • Export Citation
  • 17.

    Dustin MLGarcia-Aguilar JHibbs MLet al: Structure and regulation of the leukocyte adhesion receptor LFA-1 and its counterreceptors, ICAM-1 and ICAM-2. Cold Spring Harb Symp Quant Biol 54 Pt 2:7537651989Dustin ML Garcia-Aguilar J Hibbs ML et al: Structure and regulation of the leukocyte adhesion receptor LFA-1 and its counterreceptors ICAM-1 and ICAM-2. Cold Spring Harb Symp Quant Biol 54 Pt 2:753–765 1989

    • Search Google Scholar
    • Export Citation
  • 18.

    Dustin MLSpringer TA: Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol 107:3213311988Dustin ML Springer TA: Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol 107:321–331 1988

    • Search Google Scholar
    • Export Citation
  • 19.

    Endo SBranson PJAlksne JF: Experimental model of symptomatic vasospasm in rabbits. Stroke 19:142014251988Endo S Branson PJ Alksne JF: Experimental model of symptomatic vasospasm in rabbits. Stroke 19:1420–1425 1988

    • Search Google Scholar
    • Export Citation
  • 20.

    Fassbender KHodapp BRossol Set al: Endothelin-1 in subarachnoid hemorrhage: an acute-phase reactant produced by cerebrospinal fluid leukocytes. Stroke 31:297129752000Fassbender K Hodapp B Rossol S et al: Endothelin-1 in subarachnoid hemorrhage: an acute-phase reactant produced by cerebrospinal fluid leukocytes. Stroke 31:2971–2975 2000

    • Search Google Scholar
    • Export Citation
  • 21.

    Fassbender KHodapp BRossol Set al: Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry 70:5345372001Fassbender K Hodapp B Rossol S et al: Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry 70:534–537 2001

    • Search Google Scholar
    • Export Citation
  • 22.

    Gabikian PClatterbuck REEberhart CGet al: Prevention of experimental cerebral vasospasm by intracranial delivery of a nitric oxide donor from a controlled-release polymer: toxicity and efficacy studies in rabbits and rats. Stroke 33:268126862002Gabikian P Clatterbuck RE Eberhart CG et al: Prevention of experimental cerebral vasospasm by intracranial delivery of a nitric oxide donor from a controlled-release polymer: toxicity and efficacy studies in rabbits and rats. Stroke 33:2681–2686 2002

    • Search Google Scholar
    • Export Citation
  • 23.

    Handa YKubota TKaneko Met al: Expression of intercellular adhesion molecule 1 (ICAM-1) on the cerebral artery following subarachnoid haemorrhage in rats. Acta Neurochir 132:92971995Handa Y Kubota T Kaneko M et al: Expression of intercellular adhesion molecule 1 (ICAM-1) on the cerebral artery following subarachnoid haemorrhage in rats. Acta Neurochir 132:92–97 1995

    • Search Google Scholar
    • Export Citation
  • 24.

    Hubbard AKRothlein R: Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades. Free Radic Biol Med 28:137913862000Hubbard AK Rothlein R: Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades. Free Radic Biol Med 28:1379–1386 2000

    • Search Google Scholar
    • Export Citation
  • 25.

    Johnston SCDustin MLHibbs MLet al: On the species specificity of the interaction of LFA-1 with intercellular adhesion molecules. J Immunol 145:118111871990Johnston SC Dustin ML Hibbs ML et al: On the species specificity of the interaction of LFA-1 with intercellular adhesion molecules. J Immunol 145:1181–1187 1990

    • Search Google Scholar
    • Export Citation
  • 26.

    Kapiotis SSengoelge GSperr WRet al: Ibuprofen inhibits pyrogen-dependent expression of VCAM-1 and ICAM-1 on human endothelial cells. Life Sci 58:216721811996Kapiotis S Sengoelge G Sperr WR et al: Ibuprofen inhibits pyrogen-dependent expression of VCAM-1 and ICAM-1 on human endothelial cells. Life Sci 58:2167–2181 1996

    • Search Google Scholar
    • Export Citation
  • 27.

    Liles WCDale DCPrice THet al: Inhibition of in vivo neutrophil transmigration by a novel humanized anti-CD11/CD18 monoclonal antibody. Cytokines Cell Mol Ther 6:1211262000Liles WC Dale DC Price TH et al: Inhibition of in vivo neutrophil transmigration by a novel humanized anti-CD11/CD18 monoclonal antibody. Cytokines Cell Mol Ther 6:121–126 2000

    • Search Google Scholar
    • Export Citation
  • 28.

    Macdonald RLWeir B (eds): Animal models. Cerebral Vasospasm. San Diego: Academic Press2001 pp 449475Macdonald RL Weir B (eds): Animal models. Cerebral Vasospasm. San Diego: Academic Press 2001 pp 449–475

    • Search Google Scholar
    • Export Citation
  • 29.

    Mack WJMocco JHoh DJet al: Outcome prediction with serum intercellular adhesion molecule-1 levels after aneurysmal subarachnoid hemorrhage. J Neurosurg 96:71752002Mack WJ Mocco J Hoh DJ et al: Outcome prediction with serum intercellular adhesion molecule-1 levels after aneurysmal subarachnoid hemorrhage. J Neurosurg 96:71–75 2002

    • Search Google Scholar
    • Export Citation
  • 30.

    Marlin SDSpringer TA: Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell 51:8138191987Marlin SD Springer TA: Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1). Cell 51:813–819 1987

    • Search Google Scholar
    • Export Citation
  • 31.

    Megyesi JFVollrath BCook DAet al: In vivo animal models of cerebral vasospasm: a review. Neurosurgery 46:4484612000Megyesi JF Vollrath B Cook DA et al: In vivo animal models of cerebral vasospasm: a review. Neurosurgery 46:448–461 2000

    • Search Google Scholar
    • Export Citation
  • 32.

    Mocco JMack WJKim GHet al: Rise in serum soluble intercellular adhesion molecule-1 levels with vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg 97:5375412002Mocco J Mack WJ Kim GH et al: Rise in serum soluble intercellular adhesion molecule-1 levels with vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg 97:537–541 2002

    • Search Google Scholar
    • Export Citation
  • 33.

    Mori TNagata KTown Tet al: Intracisternal increase of super-oxide anion production in a canine subarachnoid hemorrhage model. Stroke 32:6366422001Mori T Nagata K Town T et al: Intracisternal increase of super-oxide anion production in a canine subarachnoid hemorrhage model. Stroke 32:636–642 2001

    • Search Google Scholar
    • Export Citation
  • 34.

    Nakagomi TKassell NFSasaki Tet al: Impairment of endothelium-dependent vasodilation induced by acetylcholine and adenosine triphosphate following experimental subarachnoid hemorrhage. Stroke 18:4824891987Nakagomi T Kassell NF Sasaki T et al: Impairment of endothelium-dependent vasodilation induced by acetylcholine and adenosine triphosphate following experimental subarachnoid hemorrhage. Stroke 18:482–489 1987

    • Search Google Scholar
    • Export Citation
  • 35.

    Nielsen VGWebster RO: Inhibition of human polymorphonuclear leukocyte functions by ibuprofen. Immunopharmacology 13:61711987Nielsen VG Webster RO: Inhibition of human polymorphonuclear leukocyte functions by ibuprofen. Immunopharmacology 13:61–71 1987

    • Search Google Scholar
    • Export Citation
  • 36.

    Nissen JJMantle DBlackburn Aet al: The selectin superfamily: the role of selectin adhesion molecules in delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage. Acta Neurochir Suppl 76:55602000Nissen JJ Mantle D Blackburn A et al: The selectin superfamily: the role of selectin adhesion molecules in delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage. Acta Neurochir Suppl 76:55–60 2000

    • Search Google Scholar
    • Export Citation
  • 37.

    Offerhaus Lvan Gool J: Electrocardiographic changes and tissue catecholamines in experimental subarachnoid haemorrhage. Cardiovasc Res 3:4334401969Offerhaus L van Gool J: Electrocardiographic changes and tissue catecholamines in experimental subarachnoid haemorrhage. Cardiovasc Res 3:433–440 1969

    • Search Google Scholar
    • Export Citation
  • 38.

    Oshiro EMHoffman PADietsch GNet al: Inhibition of experimental vasospasm with anti-intercellular adhesion molecule-1 monoclonal antibody in rats. Stroke 28:203120381997Oshiro EM Hoffman PA Dietsch GN et al: Inhibition of experimental vasospasm with anti-intercellular adhesion molecule-1 monoclonal antibody in rats. Stroke 28:2031–2038 1997

    • Search Google Scholar
    • Export Citation
  • 39.

    Osuka KSuzuki YWatanabe Yet al: Inducible cyclooxygenase expression in canine basilar artery after experimental subarachnoid hemorrhage. Stroke 29:121912221998Osuka K Suzuki Y Watanabe Y et al: Inducible cyclooxygenase expression in canine basilar artery after experimental subarachnoid hemorrhage. Stroke 29:1219–1222 1998

    • Search Google Scholar
    • Export Citation
  • 40.

    Polin RSBavbek MShaffrey MEet al: Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage. J Neurosurg 89:5595671998Polin RS Bavbek M Shaffrey ME et al: Detection of soluble E-selectin ICAM-1 VCAM-1 and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage. J Neurosurg 89:559–567 1998

    • Search Google Scholar
    • Export Citation
  • 41.

    Rusnak JMKopecky SLClements IPet al: An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study). Am J Cardiol 88:4824872001Rusnak JM Kopecky SL Clements IP et al: An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study). Am J Cardiol 88:482–487 2001

    • Search Google Scholar
    • Export Citation
  • 42.

    Sercombe RDinh YRGomis P: Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn J Pharmacol 88:2272492002Sercombe R Dinh YR Gomis P: Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn J Pharmacol 88:227–249 2002

    • Search Google Scholar
    • Export Citation
  • 43.

    Sethi SSharma PDikshit M: Nitric oxide- and oxygen-derived free radical generation from control and lipopolysaccharide-treated rat polymorphonuclear leukocyte. Nitric Oxide 5:4824932001Sethi S Sharma P Dikshit M: Nitric oxide- and oxygen-derived free radical generation from control and lipopolysaccharide-treated rat polymorphonuclear leukocyte. Nitric Oxide 5:482–493 2001

    • Search Google Scholar
    • Export Citation
  • 44.

    Sills AK JrClatterbuck REThompson RCet al: Endothelial cell expression of intercellular adhesion molecule 1 in experimental posthemorrhagic vasospasm. Neurosurgery 41:4534611997Sills AK Jr Clatterbuck RE Thompson RC et al: Endothelial cell expression of intercellular adhesion molecule 1 in experimental posthemorrhagic vasospasm. Neurosurgery 41:453–461 1997

    • Search Google Scholar
    • Export Citation
  • 45.

    Smith CWMarlin SDRothlein Ret al: Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J Clin Invest 83:200820171989Smith CW Marlin SD Rothlein R et al: Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J Clin Invest 83:2008–2017 1989

    • Search Google Scholar
    • Export Citation
  • 46.

    Springer TGalfre GSecher DSet al: Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol 9:3013061979Springer T Galfre G Secher DS et al: Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol 9:301–306 1979

    • Search Google Scholar
    • Export Citation
  • 47.

    Springer TA: Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol 57:8278721995Springer TA: Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol 57:827–872 1995

    • Search Google Scholar
    • Export Citation
  • 48.

    Springer TADustin MLKishimoto TKet al: The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol 5:2232521987Springer TA Dustin ML Kishimoto TK et al: The lymphocyte function-associated LFA-1 CD2 and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol 5:223–252 1987

    • Search Google Scholar
    • Export Citation
  • 49.

    Staunton DEMarlin SDStratowa Cet al: Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 52:9259331988Staunton DE Marlin SD Stratowa C et al: Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 52:925–933 1988

    • Search Google Scholar
    • Export Citation
  • 50.

    Thai QAOshiro EMTamargo RJ: Inhibition of experimental vasospasm in rats with the periadventitial administration of ibuprofen using controlled-release polymers. Stroke 30:1401471999Thai QA Oshiro EM Tamargo RJ: Inhibition of experimental vasospasm in rats with the periadventitial administration of ibuprofen using controlled-release polymers. Stroke 30:140–147 1999

    • Search Google Scholar
    • Export Citation
  • 51.

    Van der Vieren MCrowe DTHoekstra Det al: The leukocyte integrin αDβ2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1. J Immunol 163:198419901999Van der Vieren M Crowe DT Hoekstra D et al: The leukocyte integrin αDβ2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1. J Immunol 163:1984–1990 1999

    • Search Google Scholar
    • Export Citation
  • 52.

    Yenari MAKunis DSun GHet al: Hu23F2G, an antibody recognizing the leukocyte CD11/CD18 integrin, reduces injury in a rabbit model of transient focal cerebral ischemia. Exp Neurol 153:2232331998Yenari MA Kunis D Sun GH et al: Hu23F2G an antibody recognizing the leukocyte CD11/CD18 integrin reduces injury in a rabbit model of transient focal cerebral ischemia. Exp Neurol 153:223–233 1998

    • Search Google Scholar
    • Export Citation
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