Lack of platelet endothelial cell adhesion molecule-1 attenuates foreign body inflammation because of decreased angiogenesis.
Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a 130-kd member of the immunoglobulin superfamily of proteins, expressed on endothelial cells, leukocytes, and platelets. Antibody-blocking studies have implicated it in modulating leukocyte transmigration and angiogenesis. However, the generation of the PECAM-1 knockout mouse has shown that its function can be compensated for by similarly acting proteins because most acute inflammatory models proceed in a comparable manner in wild-type and knockout animals. We decided to examine the function of PECAM-1 in the chronic process of foreign body inflammation. We show that PECAM-1-deficient mice exhibit attenuated neutrophil infiltration in and around a subcutaneous polyvinyl acetyl implant. Bone marrow engraftment studies indicate that the lack of CD31 expression on the endothelium determines the diminished leukocyte accumulation in the knockout implants. Specifically, we find that decreased angiogenesis (as manifested by lower vessel density, decreased hemoglobin content, and less laminin deposition) correlates with lower neutrophil accumulation in the knockout animals. This study indicates that the absence of endothelial PECAM-1 results in decreased angiogenesis and therefore in diminished delivery of leukocytes to the foreign body implants.
Solowiej
Anna
A
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Biswas
Purba
P
Graesser
Donnasue
D
Madri
Joseph A
JA
D000818:Animals; D016026:Bone Marrow Transplantation / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005547:Foreign Bodies / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D006454:Hemoglobins / Q000378:metabolism; D007249:Inflammation / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D007962:Leukocytes / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000517:prevention & control*; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics* / Q000502:physiology*; D011145:Polyvinyls; D019736:Prostheses and Implants
D006454:Hemoglobins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011145:Polyvinyls; C013215:polyvinyl acetate; D009195:Peroxidase