Permeability characteristics of hemoglobin derivatives across cultured endothelial cell monolayers

Kunihiko Nakai, Ichiro Sakuma, Toshio Ohta, Joji Ando, Akira Kitabatake, Yoshikazu Nakazato, Tsuneo A. Takahashi

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

To better understand the vascular activity of hemoglobin-based (Hb-based) oxygen carriers, the endothelial permeability characteristics of Hb derivatives having various molecular masses were defined by using monolayers of bovine endothelial cells cultured on microporous membranes. The endothelial permeability of unmodified bovine Hb was almost twice that of bovine serum albumin. Intramolecularly cross-linked human Hb showed slightly but significantly reduced permeability as compared with unmodified bovine Hb. Polyethyleneglycol modification or haptoglobin binding to Hb further reduced the permeability. These properties were intensified in conditions in which the endothelial barrier function was reduced by pretreatment with either interleukin-6 (100 ng/mL, 21 hours) or lipopolysaccharide (1 μg/mL, 10 hours). In contrast, there was little permeability of liposome-encapsulated Hb, and it was almost unaffected by the pretreatments. These data provide the first information that Hb derivatives with smaller molecular masses show larger transendothelial flux. Because Hb is a potent scavenger of endothelium-derived relaxing factor (EDRF), our observations support the idea that smaller Hb-based acellular oxygen carriers are potent vasoconstrictors as a result of abluminal EDRF scavenging.

Original languageEnglish
Pages (from-to)313-319
Number of pages7
JournalJournal of Laboratory and Clinical Medicine
Volume132
Issue number4
DOIs
Publication statusPublished - 1998 Oct

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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