Cd18 but Not P-Selectin Blockade Increases Incidence and Severity of Subcutaneous E Coli Abscess Formation

Talbott, G. Douglas; Sharar, Sam R.; Paulson, James C.; Harlan, John M.; Winn, Robert K.

doi:10.1097/00003246-199304001-00194

Cited by 3 publications

(5 citation statements)

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“…The above results are in sharp contrast to previous work in which administration of MAb to CD18 resulted in significant weight loss, prolonged febrile reactions, and increased incidence and severity of abscess formation (including transdermal necrosis) in animals given injections of gram-positive and gram-negative bacteria (8,16,19). By specifically inhibiting CD11a and L-selectin, we have further examined the impact of MAbs to adhesion molecules on the susceptibility to cutaneous abscess formation.…”

Section: Discussioncontrasting

confidence: 75%

“…Sharar et al used a rabbit model of soft tissue infection by Staphylococcus aureus inoculation and reported that inhibition of WBC adherence by the anti-CD18 MAb 60.3 resulted in substantial increases in incidence and severity of infection compared with those in controls given saline (16). The same authors have also reported that there was no effect on susceptibility to peritoneal or soft tissue infection when P-selectin was blocked with the MAb PB1.3 (19). Consistent with these results, we have previously reported that MAbs to CD18 (R15.7) significantly increase the susceptibility to dermal abscess formation by S. aureus and Pseudomonas aeruginosa.…”

supporting

confidence: 87%

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Differential effects of monoclonal antibody blockade of adhesion molecules on in vivo susceptibility to soft tissue infection

1995

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Leukocyte adherence to endothelial cells has been implicated in the pathogenesis of microvascular injury as well as in host defense against various infectious microorganisms. Administration of monoclonal antibodies directed against the ␤ chain of the leukocyte integrins inhibits leukocyte-endothelial-cell adherence and has been reported to modulate ischemia-reperfusion and inflammatory injury. However, such inhibition of adhesion molecule function adversely affects resistance to infection. The following studies were carried out to determine whether monoclonal antibodies to other adhesion molecules, including L-selectin (CD62L), and CD11a (the ␣ chain of LFA-1), also increase susceptibility to infection. New Zealand White rabbits were shaved and given subcutaneous injections on their dorsa with 10 9 CFU of Staphylococcus aureus ATCC 25923 at two sites and with 10 8 CFU at two sites. A second set of rabbits were given subcutaneous injections with 10 8 CFU of P. aeruginosa ATCC 27853 at two sites and with 10 7 CFUs at two sites. The animals were monitored for 1 week. There were three blinded experimental groups: controls given saline and two groups given blocking monoclonal antibodies to either L-selectin (Dreg-200) or CD11a (R7.1). In contrast to monoclonal antibodies to CD18, none of the monoclonal antibodies significantly increased the risk of abscess formation by S. aureus, although inhibition of CD11a increased the rate of abscess formation by P. aeruginosa.

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Section: Discussioncontrasting

confidence: 75%

supporting

confidence: 87%

Differential effects of monoclonal antibody blockade of adhesion molecules on in vivo susceptibility to soft tissue infection

1995

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“…The majority of these studies have focused on /32 integrin and ICAM-1 blockade, in most cases showing some amelioration of injury, with the magnitude of effect dependent on both type of injury and organ system involved. Second, studies assessing the effect of/32 integrin blockade on bacterial host defense demonstrate a spectrum of impaired immune defense against bacterial infection, ranging from minimal [75] to intermediate [110] to severe [123], in agreement with the phenotype of congential /32 integrin deficiency found in humans [5,16]. Two points regarding the potential clinical efficacy and safety of/32 integrin blockade deserve emphasis, however.…”

Section: Act I Vat I Ng ~ Ant I Sense Agent S ~ ~L Eeul Es O~gonucl mentioning

confidence: 73%

“…With regards to ischemia-reperfusion, it is noteworthy that in identical experimental systems in which /32 integrin [130], P- [136], or L-selectin [74] -mediated adherence have been inhibited independently, the degree of protection from injury is similar. Regarding immune defense and monoclonal antibody inhibition of selectins, early data suggest that P-selectin blockade may result in less risk of bacterial infections [111] compared to/32 integrin blockade [110,123]. The question of whether combined selectin and integrin blockade will further improve outcome in injuries where blockade of each alone has had only partial protective effect has yet to be addressed.…”

Section: Act I Vat I Ng ~ Ant I Sense Agent S ~ ~L Eeul Es O~gonucl mentioning

confidence: 99%

The adhesion cascade and anti-adhesion therapy: an overview

Sharar

Winn

Harlan

1995

Springer Semin Immunopathol

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“…In the absence of infection, CD11/18 inhibition in most studies reduces inflammatory tissue injury and improves outcome (4,15,17,25,45). However, in models employing infectious challenges, inhibiting CD11/18 has frequently been detrimental (9,12,34,35,38,40). Similarly, our laboratory found that inhibiting CD11b during inflammatory injury in the absence of infection [e.g., tumor necrosis factor (TNF) challenge in canines], improved lung injury and survival (8).…”

mentioning

confidence: 92%

ICAM-1 and CD11b inhibition worsen outcome in rats withE. colipneumonia

Zéni

Parent

Correa

et al. 1999

Journal of Applied Physiology

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We investigated whether inhibiting an endothelial adhesion molecule [intracellular adhesion molecule 1 (ICAM-1)] would alter outcome and lung injury in a similar fashion to inhibition of a leukocyte adhesion molecule (integrin CD11b) in a rat model of gram-negative pneumonia. Inhibition of ICAM-1 with monoclonal antibody (MAb) 1A29 (1 mg/kg sc or 0.2 or 2 mg/kg iv, q 12 h x 3) or of CD11b with MAb 1B6 (1 mg/kg sc, q 12 h x 3) were compared against similarly administered placebo proteins in rats challenged with intrabronchial Escherichia coli. After challenge, all animals were treated with antibiotics. ICAM-1 MAb (6 mg/kg, iv, total dose) increased mortality vs. control (P = 0.03). CD11b MAb (3 mg/kg, sc, total dose) did not significantly (P = 0.16) increase mortality rates, but this was not in a range of probability to exclude a harmful effect. All other doses of MAb had no significant effect on survival rates. ICAM-1 and CD11b MAbs had significantly different effects on the time course of lung injury, circulating white cells and lymphocytes, and lung lavage white cells and neutrophils (P = 0.04-0.003). CD11b MAb decreased, whereas ICAM-1 MAb increased these measures compared with control from 6 to 12 h after E. coli. However, from 144 to 168 h after E. coli both MAbs increased these measures compared with control rats but to a greater level with CD11b MAb. Thus both ICAM-1 and CD11b appear to be necessary for survival during E. coli pneumonia. Although these adhesion molecules may participate differently in early lung injury, with CD11b increasing and ICAM-1 decreasing inflammation and injury, both are important for the resolution of later injury. During gram-negative pneumonia the protective roles of ICAM-1 and CD11b may make their therapeutic inhibition difficult.

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Cd18 but Not P-Selectin Blockade Increases Incidence and Severity of Subcutaneous E Coli Abscess Formation

Cited by 3 publications

References 0 publications

Differential effects of monoclonal antibody blockade of adhesion molecules on in vivo susceptibility to soft tissue infection

Differential effects of monoclonal antibody blockade of adhesion molecules on in vivo susceptibility to soft tissue infection

The adhesion cascade and anti-adhesion therapy: an overview

ICAM-1 and CD11b inhibition worsen outcome in rats withE. colipneumonia

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