Activation of human endothelial cells by mobilized porcine leukocytes in vitro

Abstract

Porcine PBPC activate HUVEC, as suggested by an increase in surface E-selectin, VCAM-1, and ICAM-1 levels, and have a maximum effect after 9 hr. Freezing of PBPC does not affect PBPC-induced activation of HUVEC. PBL induce greater activation of HUVEC than do PBPC. CD2- cells are primarily responsible for PBPC-induced activation of HUVEC and direct cell-cell contact is required. Removal of CD2- cells before the administration of PBPC or the use of agents that interrupt PBPC-endothelial cell interactions may prevent or treat TM in baboons.

E-Selectin Early Overexpression Induced by Allogeneic Activation in Isolated Mouse Lung

“…Our results are in agreement with Fries et al (42) who reported the maximal transcript levels both for VCAM-1 and for E-selectin at 3 to 6 hours in various mouse tissues after lipopolysaccharide administration. They are in keeping with Appel et al (43) who demonstrated in a xenogeneic in vitro model that porcine peripheral blood lymphocytes induced high levels of E-selectin and VCAM-1 after direct cell-cell contact. TNF-␣ is known to induce ICAM-1, VCAM-1, and E-selectin expression in EC cultures (44 -47).…”

Relative effects of GAL+ and GALlow/− porcine hematopoietic cells on primate platelet aggregation and endothelial cell activation: implications for the induction of mixed hematopoietic chimerism in the pig‐to‐primate model

“…Using the HUVEC assay with a transwell membrane permeable to cytokines but not to PBPC, Appel et al demonstrated that direct cell–cell contact is also required for the activation of HUVEC by PBPC [8]. Furthermore, Benatuil et al recently showed that peripheral blood mononuclear cells, but not activated HUVEC or culture supernatant of activated HUVEC, are able to generate thrombin when added to defibrinated human plasma [18].…”

“…The extent of PBPC‐induced activation of HUVEC is dependent on the duration of time for which these cells are permitted to interact [8]. VCAM‐1, ICAM‐1, and E‐selectin expression on HUVEC were increased as early as 3 h after the addition of Gal + PBPC, with maximum levels being reached after approximately 9 h. Expression then remained stable for at least 24 h. The incubation of HUVEC with PBPC or BM cells in the current experiments was discontinued after 14 to 16 h in order to assess the effect of maximal stimulation.…”

“…The HUVEC culture and measurement of E‐selectin, ICAM‐1 and VCAM‐1 expression by enzyme‐linked immunosorbent assay (ELISA) have been described previously by Appel et al [8]. Tumor necrosis factor‐ α (10 ng/ml final concentration) was used as a positive control.…”

“…In vitro investigations by Alwayn and Appel and their respective colleagues demonstrated that the infused pig cells were directly responsible for the platelet aggregation and resulting thrombocytopenia [6,7]. Furthermore, Appel et al demonstrated that PBPC can directly activate human umbilical vein endothelial cells (HUVEC) [8].…”