Cg. Elias et al., LIGATION OF CD31 PECAM-1 MODULATES THE FUNCTION OF LYMPHOCYTES, MONOCYTES AND NEUTROPHILS/, European Journal of Immunology, 28(6), 1998, pp. 1948-1958
CD31 or platelet/endothelial cell adhesion molecule (PECAM-1) is a 130
-kDa glycoprotein expressed on endothelial cells, granulocytes, a subs
et 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 ly
mphocyte proliferation to suboptimal doses of anti-CD31 mAb. This prol
iferation is accompanied by secretion of numerous cytokines and chemok
ines, up-regulation of CD25 and an increase in cell size. Purification
of T lymphocytes into CD45RO and CD45RA subsets showed that only naiv
e CD45RA T lymphocytes are co-stimulated by anti-CD31 mAb. Further stu
dies on neutrophils show that engagement of CD31 results in down-regul
ation of CD62L and up-regulation of CD11b/CD18 as well as oxidative bu
rst, 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-depe
ndent kinases are involved in monocyte activation via CD31. Of the fou
r mAb used in this study, only two activated human leukocytes. These m
Ab 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.