title: Co-ligation of CD31 and Fc gamma RII induces cytokine production in human monocytes.
abstract: The CD31 (PECAM-1) cell surface glycoprotein is considered to be involved in intercellular recognition and adhesion. Cytokines play a major role in cellular interactions, and therefore it was of interest to study whether engagement of CD31 affects synthesis and release of proadhesive cytokines. Here we demonstrate that immobilized CD31 mAb 1B5 induces the release of TNF-alpha, IL-1 beta, and IL-8 from human PBMCs. CD11b mAb VIM12 and HLA-D mAb VID1, both of which are of the same Ig subclass as mAb 1B5 (IgG1), as well as nonbinding isotype control mAb VIAP, were ineffective. That the effect was caused by the mAb, but not endotoxin 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 blocked by soluble F(ab) fragments of anti-IgG Fc gamma RII mAb IV.3, suggesting a significant contribution of that FcR. Cross-linking of neither 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 preparations were coated concomitantly. Therefore, only coligation of CD31 and Fc gamma RII appears to transduce activation signals leading to cytokine production. Our findings thus indicate a novel functional aspect of CD31 molecules that might play an important role in the propagation of an ongoing immune response as well as in the regulation of cell-cell interactions during inflammatory reactions.
authors.affiliation: Institute of Immunology, University of Vienna, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: Knapp
authors.forename: O
authors.initials: O
authors.lastname: Majdic
authors.forename: H
authors.initials: H
authors.lastname: Stockinger
authors.forename: G A
authors.initials: GA
authors.lastname: Böhmig
authors.forename: G J
authors.initials: GJ
authors.lastname: Zlabinger
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011940:Receptor Aggregation; D017452:Receptors, IgG / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha