CO-LIGATION OF CD31 AND FC-GAMMA-RII INDUCES CYTOKINE PRODUCTION IN HUMAN MONOCYTES

The CD31 (PECAM-1) cell surface glycoprotein is considered to be invol ved in intercellular recognition and adhesion. Cytokines play a major role in cellular interactions, and therefore it was of interest to stu dy whether engagement of CD31 affects synthesis and release of proadhe sive cytokines. Here we demonstrate that immobilized CD31 mAb 1B5 indu ces the release of TNF-alpha, IL-1 beta, and IL-8 from human PBMCs. CD 11b mAb VIM12 and HLA-D mAb VID1, both of which are of the same Ig sub class as mAb 1B5 (IgG1), as well as nonbinding isotype control mAb VIA P, were ineffective. That the effect was caused by the mAb, but not en dotoxin contamination, was shown by negative Limulus amebocyte lysate tests and coculture with polymyxin B, which did not abolish TNF-alpha release. Cytokine production through intact mAb 1B5 was completely blo cked by soluble F(ab) fragments of anti-IgG Fc gamma RII mAb IV.3, sug gesting a significant contribution of that FcR. Cross-linking of neith er CD31 nor Fc gamma RII molecules with the respective F(ab) fragments induced TNF-alpha release, but nonbinding control IgG1 Ab was able to restore the response of PBMC to 1B5 F(ab) fragments, when both Ab pre parations were coated concomitantly. Therefore, only coligation of CD3 1 and Fc gamma RII appears to transduce activation signals leading to cytokine production. Our findings thus indicate a novel functional asp ect of CD31 molecules that might play an important role in the propaga tion of an ongoing immune response as well as in the regulation of cel l-cell interactions during inflammatory reactions.