Characterization of a Novel Adhesion Function Blocking Monoclonal Antibody to Rat/Mouse P-Selectin Generated in the P-Selectin-Deficient Mouse

Walter, Ulrike; Ayer, Linda M.; Wolitzky, Barry A.; Wagner, Denisa D.; Hynes, Richard O.; Manning, Anthony M.; Issekutz, Andrew C.

doi:10.1089/hyb.1997.16.249

Cited by 64 publications

(40 citation statements)

References 30 publications

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“…The hamster IgG mAb HM␣ 5 reacts with and blocks the rat ␣ 5 of VLA-5 (27,28) and HRL-3 (a gift from D. Anderson, Pharmacia Upjohn, Kalamazoo, MI, and M. Miyasaka, Osaka University) reacts with and blocks rat L-selectin (29). The mouse IgG2a mAb RMP-1 recognizes and blocks rat P-selectin, and the mouse IgG1 mAb RME-1 blocks rat E-selectin (30,31). These were generated in our laboratory.…”

Section: Mab Treatmentsmentioning

confidence: 99%

The α4β1 (Very Late Antigen (VLA)-4, CD49d/CD29) and α5β1 (VLA-5, CD49e/CD29) Integrins Mediate β2 (CD11/CD18) Integrin-Independent Neutrophil Recruitment to Endotoxin-Induced Lung Inflammation

Burns

Issekutz

Yagita

et al. 2001

The Journal of Immunology

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The β2 integrin cell adhesion molecules (CAM) mediate polymorphonuclear leukocyte (PMNL) emigration in most inflamed tissues, but, in the lung, other yet to be identified CAMs appear to be involved. In Lewis rats, the intratracheal injection of Escherichia coli-LPS induced acute (6-h) PMNL accumulation in the lung parenchyma (280 × 106 by myeloperoxidase assay; PBS control = 35 × 106) and bronchoalveolar lavage fluid (BALF = 27 × 106; PBS = 0.1 × 106). Parenchymal accumulation was not inhibited by a blocking Ab to β2 integrins and only minimally inhibited (20.5%; p < 0.05) in BALF. We examined the role of α4β1 and α5β1 integrins and of selectins in this PMNL recruitment. Treatment with mAbs to α4β1 or α5β1, even in combination, had no effect on PMNL accumulation induced by intratracheal LPS. However, anti-α4 combined with anti-β2 mAbs inhibited PMNL recruitment to the parenchyma by 56% (p < 0.001) and to BALF by 58% (p < 0.01). The addition of anti-α5 mAb to β2 plus α4 blockade inhibited PMNL accumulation further (by 79%; p < 0.05). In contrast, blockade of L-, P-, and E-selectins in combination or together with β2, α4, and α5 integrins had no effect. LPS-induced BALF protein accumulation was not inhibited by treatment with anti-β2 plus α4 mAbs, but was prevented when α5β1 was also blocked. Thus, while selectins appear to play no role, α4β1 and α5β1 function as major alternate CAMs to the β2 integrins in mediating PMNL migration to lung and to pulmonary vascular and epithelial permeability.

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Section: Mab Treatmentsmentioning

confidence: 99%

The α4β1 (Very Late Antigen (VLA)-4, CD49d/CD29) and α5β1 (VLA-5, CD49e/CD29) Integrins Mediate β2 (CD11/CD18) Integrin-Independent Neutrophil Recruitment to Endotoxin-Induced Lung Inflammation

Burns

Issekutz

Yagita

et al. 2001

The Journal of Immunology

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“…The monoclonal antibodies (MAb) used were RMP-1, a murine immunoglobulin G 2a (IgG 2a ) against rat and mouse P-selectin [14], and RME-1, a murine IgG 1 against rat and mouse E-selectin [15]. The control immunoglobulines used were UPC-10, a nonbinding murine IgG 2a (Sigma Química, Madrid, Spain) [16], and P23, a nonbinding murine IgG 1 directed against human (but not mouse) P-selectin [17].…”

Section: Quantification Of P-and E-selectin Expressionmentioning

confidence: 99%

Role of P‐selectin in radiation‐induced intestinal inflammatory damage

Mollà

Gironella

Salas

et al. 2001

Intl Journal of Cancer

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SUMMARY The aims of our study were to characterize the dose-and time-dependent changes in endothelial P-selectin expression and the role of this adhesion molecule as a mediator of radiation-induced inflammation. For that purpose, endothelial P-selectin expression was measured by the radiolabeled antibody technique in control and irradiated mice at 2, 6, and 24 hr following abdominal irradiation with 4 or 10 Gy; leukocyte endothelial cell interactions were assessed using intravital microscopy in intestinal venules following irradiation at the aforementioned doses and times in C57BL/6 and P-selectindeficient mice. In wild-type mice, radiation induced a time-and dose-dependent upregulation of P-selectin and a significant increase in the flux of rolling leukocytes 2 hr after irradiation. Irradiation induced a significant increase in leukocyte adhesion that was dosedependent. Following irradiation, P-selectin-deficient mice did not show any increase in leukocyte rolling but did demonstrate a response in leukocyte adhesion similar to that of the wild-type mice. Radiation-induced dose-dependent histological inflammatory damage that did not differ between P-selectin-deficient and wild-type mice. We conclude that P-selectin is up-regulated following irradiation and is a key molecular determinant of leukocyte rolling but not leukocyte adhesion in this inflammatory condition. Therefore, isolated neutralization of this adhesion molecule is not an effective means for preventing radiation-induced inflammation.

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“…The mAbs used for the in vivo assessment of endothelial P-selectin were RMP-1, a murine immunoglobulin against rat and mouse P-selectin, 14 and P-23, a nonbinding murine immunoglobulin directed against human (but not rat) P-selectin. 15 All mAbs were scaled up and purified by protein A/G chromatography at Pharmacia-Upjohn Laboratories (Kalamazoo, MI).…”

Section: Quantification Of P-selectin Expressionmentioning

confidence: 99%

Impaired mesenteric leukocyte recruitment in experimental portal hypertension in the rat

et al. 1999

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Increased incidence of septic complications in human and experimental portal hypertension has been documented. Because development of an inflammatory response is essential in defense against infectious agents, the aim of this study was to assess leukocyte-endothelial cell interactions in an experimental model of portal hypertension. Intravital microscopy studies showed that under baseline conditions, leukocyte rolling, adhesion, and emigration in mesenteric venules were similar in control, sham operated (SO), and partial portal vein ligated (PPVL) rats. Compared with either control or SO rats, PPVL animals exhibited a markedly reduced recruitment of rolling, adherent, and emigrated leukocytes in response to leukotriene B 4 (LTB 4 ) stimulation. Similarly, platelet-activating factor (PAF) superfusion, which induced a large increment in leukocyte rolling and adherence in control and SO rats, was without any effect in PPVL animals. Endothelial P-selectin expression in control rats, as measured by the double radio-labeled monoclonal antibody (mAb) technique, was not modified by LTB 4 , but significantly increased in response to PAF. PPVL rats had a significantly lower expression of P-selectin after stimulation with PAF. Neutrophils isolated from PPVL rats exhibited increased L-selectin shedding and CD11b up-regulation in response to PAF and LTB 4 , compared with neutrophils isolated from SO rats. These observations indicate that portal hypertension is associated with a defective inflammatory response, which is manifested as a decreased recruitment of rolling leukocytes, and subsequently reduced adhesion/emigration. This defect appears to result from a reduced endothelial P-selectin up-regulation and increased L-selectin shedding. (HEPATOLOGY 1999;30:445-453.)Patients with liver disease and portal hypertension are predisposed to develop spontaneous infections by enteric bacteria. These infective sequelae are responsible for serious and often fatal complications; however, the mechanism(s) underlying this high incidence of infection-related complications is not completely understood. One potential contributing factor is impaired neutrophil function. Neutrophilic superoxide anion production and the generation of both platelet-activating factor (PAF) and leukotriene B 4 (LTB 4 ) are reduced in alcohol-related 1 and non-alcohol-related cirrhosis. 2 In addition, demonstration of bacterial translocation to mesenteric ganglia in animal models of portal hypertension without liver disease 3,4 and the appearance of a unique septic complication such as spontaneous bacterial peritonitis in human cirrhosis with portal hypertension 5 suggest that there is a deficient host immune response in the mesenteric circulation directly related to portal hypertension.The adhesion of leukocytes to vascular endothelial cells is a critical early step in the development of an inflammatory response. This process is essential in isolating and eliminating infectious agents and in tissue repair. The inflammatory response involves sequential leukocyte...

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Characterization of a Novel Adhesion Function Blocking Monoclonal Antibody to Rat/Mouse P-Selectin Generated in the P-Selectin-Deficient Mouse

Cited by 64 publications

References 30 publications

The α4β1 (Very Late Antigen (VLA)-4, CD49d/CD29) and α5β1 (VLA-5, CD49e/CD29) Integrins Mediate β2 (CD11/CD18) Integrin-Independent Neutrophil Recruitment to Endotoxin-Induced Lung Inflammation

The α4β1 (Very Late Antigen (VLA)-4, CD49d/CD29) and α5β1 (VLA-5, CD49e/CD29) Integrins Mediate β2 (CD11/CD18) Integrin-Independent Neutrophil Recruitment to Endotoxin-Induced Lung Inflammation

Role of P‐selectin in radiation‐induced intestinal inflammatory damage

Impaired mesenteric leukocyte recruitment in experimental portal hypertension in the rat

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