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Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 671-675
Macrophage inflammatory protein 1-alpha is a potential osteoclast
stimulatory factor in multiple myeloma
Sun Jin Choi,
Jose C. Cruz,
Fiona Craig,
Hoyeon Chung,
Rowena D. Devlin,
G. David Roodman, and
Melissa Alsina
From the Departments of Medicine/Hematology and Pathology,
University of Texas Health Science Center, San Antonio, TX; Cheil
General Hospital, Seoul, Korea; St. Francis Hospital and Medical
Center, Hartford, CT; and the General Clinical Research Center and
Research Service of the Audie L. Murphy Veterans Administration
Hospital, San Antonio, TX.
This study was designed to determine if macrophage inhibitory
protein-1 (MIP-1), a recently described osteoclast (OCL)
stimulatory factor,1 was present in marrow
from patients with multiple myeloma (MM) and possibly involved in the
bone destructive process. MIP-1, but not interleukin-1 (IL-1),
tumor necrosis factor- (TNF-), or interleukin-6 (IL-6), messenger
RNA was elevated in freshly isolated bone marrow from 3 of 4 patients
with MM compared to normal controls. Furthermore, enzyme-linked
immunosorbent assays of freshly isolated bone marrow plasma detected
increased concentrations of hMIP-1 (range, 75-7784 pg/mL) in 8 of 13 patients (62%) with active myeloma, in 3 of 18 patients (17%) with
stable myeloma (range, 75-190.3), as well as in conditioned media from
4 of 5 lymphoblastoid cell lines (LCLs) derived from patients with MM. Mildly elevated levels of MIP-1 were detected in 3 of 14 patients (21%) with other hematologic diagnoses (range, 80.2-118.3, median value of 96 pg/mL) but not in normal controls (0 of 7). MIP-1 was
not detected in the peripheral blood of any patients with MM. In
addition, recombinant hMIP-1 induced OCL formation in human
bone marrow cultures. Importantly, addition of a
neutralizing antibody to MIP-1 to human bone marrow cultures treated
with freshly isolated marrow plasma from patients with MM blocked
the increased OCL formation induced by these marrow samples but
had no effect on control levels of OCL formation. Thus,
high levels of MIP-1 are expressed in marrow samples from patients
with MM, but not in marrow from patients with other hematologic
disorders or controls, and support an important role for MIP-1 as
one of the major factors responsible for the increased OCL
stimulatory activity in patients with active MM.
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