Original Article

The role of CD11b/CD18 mediated neutrophil adhesion in complement deficient xenograft recipients

Corresponding Author

Frank M. Jakobs

n/[email protected]

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

indicates joint primary authorshipFrank M. Jakobs, M.D., Department of Pathology. The Johns Hopkins University School of Medicine, 664 D Ross Research Building, 720 Rutland Ave., Baltimore MD, 21205, USASearch for more papers by this author

Elizabeth A. Davis,

Elizabeth A. Davis

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD

indicates joint primary authorshipSearch for more papers by this author

Zhiping Qian,

Zhiping Qian

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

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David Y. Liu,

David Y. Liu

Scios Inc., Sunnyvale, CA, USA

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William M. Baldwin III,

William M. Baldwin III

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

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Fred Sanfilippo,

Fred Sanfilippo

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

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Frank M. Jakobs,

Corresponding Author

Frank M. Jakobs

n/[email protected]

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

Elizabeth A. Davis,

Elizabeth A. Davis

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD

indicates joint primary authorshipSearch for more papers by this author

Zhiping Qian,

Zhiping Qian

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

Search for more papers by this author

David Y. Liu,

David Y. Liu

Scios Inc., Sunnyvale, CA, USA

Search for more papers by this author

William M. Baldwin III,

William M. Baldwin III

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

Search for more papers by this author

Fred Sanfilippo,

Fred Sanfilippo

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

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First published: 01 October 1997

https://doi.org/10.1111/j.1399-0012.1997.tb01036.x

Citations: 4

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Abstract

Hyperacute rejection (HAR) of discordant xenografts is dependent on local complement activation. The formation of a functional complex of the complement components C5b-9 (membrane attack complex, MAC) causes endothelial injury and activation leading to coagulation and inflammation. In PVG rats which selectively lack the C6 component of complement, the MAC complex is not formed, whereas early split products of the complement cascade are produced normally. We reported previously that HAR is averted in C6 deficient xenograft recipients, and that subsequent accelerated acute rejection (AAR) can be delayed by inhibition of CD11b/CD18 (Mac-1) dependent neutrophil adhesion using leumedin, a member of a novel class of anti-inflammatory agents. Here we report the in vivo effects of a dose-response study using 2 new members of another class of Mac-1 directed agents designated nactins. Discordant cardiac xenografts from Hartley guinea pigs were heterotopically grafted into PVG(C6-) and PVG(C6+) rats. Experimental animals were divided into 3 groups receiving leumedin (group 1) or nactin (groups 2 and 3). Control animals received intravenous saline solution only. All C6(+) rats rejected their grafts hyperacutely within 10 to 15 min, irrespective of mode or dosage of treatment. C6 deficient controls rejected grafts within 17.7 ± 3.5 h (n = 10). Treatment with leumedin/nactin prolonged graft survival up to 61.0 ± 4.7 h (n = 4-6), with dose dependent differences in effectiveness among the 3 compounds tested. Histology showed that treatment was associated with less edema, hemorrhage, and neutrophil infiltrate at 2, 6, and 12 h. The marked decrease in hemorrhage seen in nactin-treated animals may reflect an interaction of Mac-1 with blood coagulation factors. Our data confirm that the neutrophil adhesion pathway is involved in AAR, especially when complement mediated injury due to MAC is restricted.

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Volume11, Issue5pt2

October 1997

Pages 516-521

The role of CD11b/CD18 mediated neutrophil adhesion in complement deficient xenograft recipients

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The role of CD11b/CD18 mediated neutrophil adhesion in complement deficient xenograft recipients

Abstract

References

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