Ligation of CD31/PECAM-1 modulates the function of lymphocytes, monocytes and neutrophils.
CD31 or platelet/endothelial cell adhesion molecule (PECAM-1) is a 130-kDa glycoprotein expressed on endothelial cells, granulocytes, a subset of lymphocytes and platelets. In this study, we examined the ability of four monoclonal antibodies (mAb) against different domains of CD31 to modulate the function of T lymphocytes, monocytes and neutrophils. Engagement of CD31 on T lymphocytes results in co-stimulation of T lymphocyte proliferation to suboptimal doses of anti-CD31 mAb. This proliferation is accompanied by secretion of numerous cytokines and chemokines, up-regulation of CD25 and an increase in cell size. Purification of T lymphocytes into CD45RO and CD45RA subsets showed that only naive CD45RA T lymphocytes are co-stimulated by anti-CD31 mAb. Further studies on neutrophils show that engagement of CD31 results in down-regulation of CD62L and up-regulation of CD11b/CD18 as well as oxidative burst, as assessed by superoxide release. In addition, ligation of CD31 on monocytes results in TNF-alpha secretion, and studies with various cell signaling inhibitors indicate that tyrosine kinases and cAMP-dependent kinases are involved in monocyte activation via CD31. Of the four mAb used in this study, only two activated human leukocytes. These mAb were PECAM-1.3 and hec7, which bind to domains 1 and 2 of CD31. We conclude that engagement of domains 1 and 2 of CD31 results in outside-in signaling in leukocytes.
Elias
C G
CG
The Department of Inflammation, Amgen Boulder Inc., USA.
Spellberg
J P
JP
Karan-Tamir
B
B
Lin
C H
CH
Wang
Y J
YJ
McKenna
P J
PJ
Muller
W A
WA
Zukowski
M M
MM
Andrew
D P
DP
D000911:Antibodies, Monoclonal / Q000276:immunology; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D048429:Cell Size; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D009000:Monocytes / Q000378:metabolism / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018925:Chemokines; D016207:Cytokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases