MECHANISMS OF CYTOMEGALOVIRUS-MEDIATED MYELOSUPPRESSION - PERTURBATION OF STROMAL CELL-FUNCTION VERSUS DIRECT INFECTION OF MYELOID CELLS

被引:199
作者
SIMMONS, P [1 ]
KAUSHANSKY, K [1 ]
TOROKSTORB, B [1 ]
机构
[1] UNIV WASHINGTON, SCH MED, SEATTLE, WA 98104 USA
关键词
D O I
10.1073/pnas.87.4.1386
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Infection with cytomegalovirus (CMV) continues to be one of the most common complications following allogeneic bone marrow transplantation. To study the role of CMV in the suppression of hemopoiesis that frequently accompanies infection, we investigated the effect of CMV on the growth of isolated committed myeloid progenitors and on hemopoiesis in long-term bone marrow cultures. Laboratory strain AD169 had no effect on the growth and development of progenitor cells. In contrast, 40% of clinical isolates of CMV inhibited colony formation by up to 100%. In long-term bone marrow cultures all CMV isolates resulted in myelosuppression, which in the majority of cases was associated with the infection of stromal elements. Analysis of RNA from stromal cells infected with AD169 and one clinical isolate demonstrated a specific deficiency of granulocyte colony-stimulating factor transcripts. For a small proportion of the clinical isolates tested in long-term bone marrow cultures, suppression of hemopoiesis was correlated with infection of developing granulocytes. These studies suggest that CMV can impair hemopoiesis either through infection of stromal cells and consequent perturbation of growth factor production or by direct infection of myeloid cells.
引用
收藏
页码:1386 / 1390
页数:5
相关论文
共 29 条
[21]  
REISNER Y, 1982, BLOOD, V59, P360
[22]   CYTOMEGALOVIRUS INFECTS HUMAN-LYMPHOCYTES AND MONOCYTES - VIRUS EXPRESSION IS RESTRICTED TO IMMEDIATE-EARLY GENE-PRODUCTS [J].
RICE, GPA ;
SCHRIER, RD ;
OLDSTONE, MBA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (19) :6134-6138
[23]   INTERACTION OF CYTOMEGALOVIRUS WITH LEUKOCYTES FROM PATIENTS WITH MONONUCLEOSIS DUE TO CYTOMEGALOVIRUS [J].
RINALDO, CR ;
BLACK, PH ;
HIRSCH, MS .
JOURNAL OF INFECTIOUS DISEASES, 1977, 136 (05) :667-678
[24]  
RINALDO CR, 1978, J IMMUNOL, V120, P130
[25]   DETECTION OF HUMAN CYTOMEGALO-VIRUS IN PERIPHERAL-BLOOD LYMPHOCYTES IN A NATURAL INFECTION [J].
SCHRIER, RD ;
NELSON, JA ;
OLDSTONE, MBA .
SCIENCE, 1985, 230 (4729) :1048-1051
[26]   HOST ORIGIN OF MARROW STROMAL CELLS FOLLOWING ALLOGENEIC BONE-MARROW TRANSPLANTATION [J].
SIMMONS, PJ ;
PRZEPIORKA, D ;
THOMAS, ED ;
TOROKSTORB, B .
NATURE, 1987, 328 (6129) :429-432
[27]  
VERDONCK LF, 1985, BLOOD, V66, P921
[28]   PURIFICATION AND BIOCHEMICAL-CHARACTERIZATION OF HUMAN PLURIPOTENT HEMATOPOIETIC COLONY-STIMULATING FACTOR [J].
WELTE, K ;
PLATZER, E ;
LU, L ;
GABRILOVE, JL ;
LEVI, E ;
MERTELSMANN, R ;
MOORE, MAS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (05) :1526-1530
[29]   HUMAN GM-CSF - MOLECULAR-CLONING OF THE COMPLEMENTARY-DNA AND PURIFICATION OF THE NATURAL AND RECOMBINANT PROTEINS [J].
WONG, GG ;
WITEK, JS ;
TEMPLE, PA ;
WILKENS, KM ;
LEARY, AC ;
LUXENBERG, DP ;
JONES, SS ;
BROWN, EL ;
KAY, RM ;
ORR, EC ;
SHOEMAKER, C ;
GOLDE, DW ;
KAUFMAN, RJ ;
HEWICK, RM ;
WANG, EA ;
CLARK, SC .
SCIENCE, 1985, 228 (4701) :810-815