A first evaluation of the natural high molecular weight polymeric Lumbricus terrestris hemoglobin as an oxygen carrier.

被引:47
作者
Hirsch, RE
Jelicks, LA
Wittenberg, BA
Kaul, DK
Shear, HL
Harrington, JP
机构
[1] YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT ANAT & STRUCT BIOL,BRONX,NY 10461
[2] YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PHYSIOL & BIOPHYS,BRONX,NY 10461
[3] MONTEFIORE MED CTR,DEPT MED,DIV HEMATOL,BRONX,NY 10467
[4] UNIV S ALABAMA,DEPT CHEM,MOBILE,AL 36688
来源
ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY | 1997年 / 25卷 / 05期
关键词
D O I
10.3109/10731199709118932
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Lumbricus terrestris hemoglobin (LtHb), an unusually stable Hb (MW similar to 4 x 10(6) Da) with respect to dissociation and oxidation, circulates extracellularly in the earthworm and at neutral pH exhibits oxygen affinity and cooperativity similar to that of human HbA. Results suggest that LtHb may serve as a model for a high molecular weight extracellular oxygen carrier. Mice and a rat model partially exchanged with LtHb showed no apparent behavioral and physical changes. P-31 NMR spectroscopy of perfused guinea pig hearts, used to assess phosphocreatine levels as an indication of the ability of LtHb to serve as an oxygen carrier to the heart, demonstrated that LtHb provides oxygen to the tissue and maintains the energy metabolism significantly better than the control non-Hb perfusion media, One day after infusion, video enhanced microscopy imaging of the mice cremaster muscle vasculature reveals temporal adhesion of leukocytes to the endothelial walls with temporal infiltration of leukocytes to the surrounding tissue, correlated with dosage. Exchanged mice rechallenged with LtHb show no overt allergic response or death. Further evaluation of this natural extracellular Hb as a potential polymeric Hb blood substitute/perfusion agent is warranted.
引用
收藏
页码:429 / 444
页数:16
相关论文
共 22 条
[1]  
BAEZ S, 1960, FLOW PROPERTIES BLOO, P122
[2]   INFLUENCE OF THE POLYMERIZATION STEP ALONE ON OXYGEN-AFFINITY AND COOPERATIVITY DURING PRODUCTION OF HYPERPOLYMERS FROM NATIVE HEMOGLOBINS WITH CROSS-LINKERS [J].
BARNIKOL, WKR .
ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY, 1994, 22 (03) :725-731
[3]  
BARNIKOL WKR, 1989, BLOOD SUBSTITUTES, P639
[4]  
FUSHITANI K, 1988, J BIOL CHEM, V263, P6502
[5]  
GIBSON QH, 1991, J BIOL CHEM, V266, P13097
[6]   SOLUTION STUDIES ON HEME PROTEINS - CIRCULAR-DICHROISM AND OPTICAL-ROTATION OF LUMBRICUS-TERRESTRIS AND GLYCERA DIBRANCHIATA-HEMOGLOBIN [J].
HARRINGT.JP ;
PANDOLFE.ER ;
HERSKOVI.TT .
BIOCHIMICA ET BIOPHYSICA ACTA, 1973, 328 (01) :61-73
[7]  
HARRINGTON JP, 1993, BLOOD, V82, pA589
[8]   INTRACELLULAR FREE MAGNESIUM AND HIGH-ENERGY PHOSPHATES IN THE PERFUSED NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RAT-HEART - A P-31 NMR-STUDY [J].
JELICKS, LA ;
GUPTA, RK .
AMERICAN JOURNAL OF HYPERTENSION, 1991, 4 (02) :131-136
[9]   P-31-NMR OF HIGH-ENERGY PHOSPHATES IN PERFUSED RAT-HEART DURING METABOLIC-ACIDOSIS [J].
JELICKS, LA ;
GUPTA, RK .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (03) :H903-H909
[10]   SCANNING-TRANSMISSION ELECTRON-MICROSCOPIC EXAMINATION OF THE HEXAGONAL BILAYER STRUCTURES FORMED BY THE REASSOCIATION OF 3 OF THE 4 SUBUNITS OF THE EXTRACELLULAR HEMOGLOBIN OF LUMBRICUS-TERRESTRIS [J].
KAPP, OH ;
MAINWARING, MG ;
VINOGRADOV, SN ;
CREWE, AV .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (21) :7532-7536