CD36 and macrophage scavenger receptor a modulate foam cell formation via inhibition of lipid-laden platelet phagocytosis.
CD34 (+) progenitor cells are a promising source of regeneration in atherosclerosis or ischemic heart disease. However, as recently published, CD34(+) progenitor cells have the potential to differentiate not only into endothelial cells but also into foam cells upon interaction with platelets. The mechanism of platelet-induced differentiation of progenitor cells into foam cells is as yet unclear. In the present study we investigated the role of scavenger receptor (SR)-A and CD36 in platelet-induced foam cell formation. Human CD34(+) progenitor cells were freshly derived from human umbilical veins and were co-incubated with platelets (2 x 10(8)/mL) up to 14 days resulting in large lipid-laden foam cells. Developing macrophages expressed SR-A, CD36, and Lox-1 as measured by fluorescent-activated cell sorting analysis. The presence of a blocking anti-CD36 or anti-SR-A antibody nearly abrogated foam cell formation, whereas anti-Lox-1 did not affect foam cell formation. Consistently blocking either anti-CD36 or anti-SR-A antibody significantly reduced the phagocytosis of lipid-laden platelets by macrophages. We conclude that CD36 and SR-A play an important role in platelet-induced foam cell formation from CD34(+) progenitor cells and thus represent a promising target to inhibit platelet-induced foam cell formation.
Seizer
Peter
P
Medizinische Klinik III, Eberhard Karls Universität Tübingen, Germany. peter.seizer@med.uni-tuebingen.de
Schiemann
Susanne
S
Merz
Tobias
T
Daub
Karin
K
Bigalke
Boris
B
Stellos
Konstantinos
K
Müller
Iris
I
Stöckle
Christina
C
Müller
Karin
K
Gawaz
Meinrad
M
May
Andreas E
AE
D018952:Antigens, CD34; D001792:Blood Platelets / Q000276:immunology*; D018955:CD36 Antigens / Q000502:physiology*; D018920:Coculture Techniques; D005487:Foam Cells / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D008055:Lipids / Q000032:analysis*; D010587:Phagocytosis; D051116:Receptors, Scavenger / Q000502:physiology*; D051117:Scavenger Receptors, Class A / Q000502:physiology
D018952:Antigens, CD34; D018955:CD36 Antigens; D008055:Lipids; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A