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Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 50-57
Stromal cell-derived factor-1 and macrophage-derived
chemokine: 2 chemokines that activate platelets
M. Anna Kowalska,
Mariusz Z. Ratajczak,
Marcin Majka,
Jianguo Jin,
Satya Kunapuli,
Lawrence Brass, and
Mortimer Poncz
From the Department of Pediatrics, Children's Hospital of
Philadelphia; the Departments of Medicine and Pediatrics, University of
Pennsylvania School of Medicine; and the Department of Physiology,
Temple University School of Medicine, Philadelphia, PA.
Platelets play roles in both thrombosis and inflammation,
and chemokines that are released at sites of inflammation could potentially activate platelets. Among the chemokine receptors expressed
on platelets, the CXCR4 is the receptor for chemokine stromal
cell-derived factor-1 (SDF-1), and the CCR4 is the receptor for
macrophage-derived chemokine (MDC). Of the chemokines tested, SDF-1 and
MDC were the only 2 that activated platelets. Both are weak agonists,
but they enhanced response to low-dose adenosine 5'-diphosphate
(ADP), epinephrine, or serotonin. When SDF-1 and MDC were added
together, full and brisk platelet aggregation occurred. Platelet
activation by these 2 chemokines appears to involve distinct pathways:
SDF-1 inhibited an increase in cyclic adenosine monophosphate (cAMP)
following prostaglandin (PG) I2, while MDC had no effect. In contrast, MDC, but not SDF-1, lead to Ca++
mobilization by platelets. Further, second-wave aggregation induced by
MDC in platelet-rich plasma was inhibited by aspirin, ADP scavenger creatine phosphate/creative phosphokinase (CP/CPK), and
ARL-66096, an antagonist of the ADP P2TAC receptor involved
in adenylyl cyclase inhibition. But the aggregation was not affected by
A3P5PS, an inhibitor of the ADP P2Y receptor. SDF-1-induced
aggregation was inhibited by aspirin, but it was only slightly affected
by CP/CPK, ARL-66096, or A3P5PS. Finally, the presence of chemokines in
platelets was determined. Reverse transcriptase-polymerase chain
reaction studies with platelet RNA did not detect the presence of SDF-1 or MDC. In summary, SDF-1 and MDC are platelet agonists that activate distinct intracellular pathways. Their importance in the development of
thrombosis at sites of inflammation needs to be further evaluated.
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