Importance of CD49d-VCAM interactions in human monocyte adhesion to porcine endothelium

P. Kwiatkowski, J. H. Artrip, J. Ankersmit, M. Schuster, R. John, S. F. Wang, N. Ma, Robert E. Michler, S. Itescu

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

By using a primate model of natural antibody depletion, we have previously shown that delayed rejection of porcine cardiac xenografts in unmodified primate recipients resulted from xenograft infiltration with monocyte/macrophage lineage cells. In the present study, we initially showed that human monocytes/macrophages demonstrated significantly greater adherence to unstimulated pig aortic endothelial cells (PAEC) than to human umbilical vein endothelial cells (HUVEC). Human TNF-alpha augmented monocyte adhesion to HUVEC by 5-fold higher levels than to PAEC. This effect could not be explained on the basis of incompatibility between human TNF-alpha and its receptor on PAEC since porcine VCAM expression increased by 75-85% after stimulation with TNF-alpha. TNF-augmented monocyte adherence was abrogated by either treatment of PAEC with an anti-VCAM Mab or monocytes with an anti- CD49d Mab. These results suggest that VCAM-CD49d interactions are important in adhesion of human monocytes to PAEC but may not be as effective as those between human monocytes and allogeneic endothelium, perhaps because of structural differences across species. Other interactions, as yet undefined, must explain the relative increase in adhesiveness of human monocytes for unstimulated PAEC versus HUVEC. In experiments investigating the functional consequences of this enhanced monocyte adherence, PAEC stimulation induced 10-fold higher levels of macrophage-derived IL-1 beta and 3-fold higher levels of T cell proliferation compared with HUVEC. Using an anti-DR Mab to interrupt antigen presentation by autologous macrophages markedly reduced the T cell proliferative response to PAEC. Together, these results indicate that the enhanced adherence of human monocytes to PAEC contributes to xenograft rejection beyond the hyperacute period by leading to tissue infiltration, elaboration of cytokines, and an augmented indirect pathway of T cell xenoantigen recognition.

Original languageEnglish (US)
Pages (from-to)67-74
Number of pages8
JournalXenotransplantation
Volume5
Issue number1
StatePublished - Feb 1998
Externally publishedYes

Fingerprint

Endothelium
Monocytes
Swine
Endothelial Cells
Human Umbilical Vein Endothelial Cells
Macrophages
Heterografts
Tumor Necrosis Factor-alpha
T-Lymphocytes
Primates
Heterophile Antigens
Adhesiveness
Interleukin-3
Antigen Presentation
Interleukin-1beta
Cell Proliferation
Cytokines
Antibodies

Keywords

  • Human monocytes
  • Porcine cardiac xenografts
  • Primate model

ASJC Scopus subject areas

  • Immunology

Cite this

Kwiatkowski, P., Artrip, J. H., Ankersmit, J., Schuster, M., John, R., Wang, S. F., ... Itescu, S. (1998). Importance of CD49d-VCAM interactions in human monocyte adhesion to porcine endothelium. Xenotransplantation, 5(1), 67-74.

Importance of CD49d-VCAM interactions in human monocyte adhesion to porcine endothelium. / Kwiatkowski, P.; Artrip, J. H.; Ankersmit, J.; Schuster, M.; John, R.; Wang, S. F.; Ma, N.; Michler, Robert E.; Itescu, S.

In: Xenotransplantation, Vol. 5, No. 1, 02.1998, p. 67-74.

Research output: Contribution to journalArticle

Kwiatkowski, P, Artrip, JH, Ankersmit, J, Schuster, M, John, R, Wang, SF, Ma, N, Michler, RE & Itescu, S 1998, 'Importance of CD49d-VCAM interactions in human monocyte adhesion to porcine endothelium', Xenotransplantation, vol. 5, no. 1, pp. 67-74.
Kwiatkowski P, Artrip JH, Ankersmit J, Schuster M, John R, Wang SF et al. Importance of CD49d-VCAM interactions in human monocyte adhesion to porcine endothelium. Xenotransplantation. 1998 Feb;5(1):67-74.
Kwiatkowski, P. ; Artrip, J. H. ; Ankersmit, J. ; Schuster, M. ; John, R. ; Wang, S. F. ; Ma, N. ; Michler, Robert E. ; Itescu, S. / Importance of CD49d-VCAM interactions in human monocyte adhesion to porcine endothelium. In: Xenotransplantation. 1998 ; Vol. 5, No. 1. pp. 67-74.
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