Platelet activation by immobilized monoclonal antibody

Evidence for a CD9 proximal signal

Lee Griffith, Joseph Slupsky, Jutta Seehafer, Lynn Boshkov, Andrew R E Shaw

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Anti-CD9 monoclonal antibodies (MoAbs) are reported to activate human platelets through stimulation of the FcγII receptor. We show here that nonstimulatory F(ab′)2 fragments of the anti-CD9 MoAb 50H.19 induce dense-granule release and dose-dependent platelet aggregation when attached to polystyrene latex beads. Cross-linking F(ab′)2 fragments of MoAb 50H. 19 by F(ab′)2 fragments of goat anti-mouse IgG does not result in platelet aggregation unless the second antibody is bound to latex beads, indicating that immobilization, and not cross-linking of the stimulus, is critical to the initiation of the CD9 signal. In contrast, F(ab′)2 fragments of the second antibody readily induce the aggrega-tion of platelets treated with the anti-FcγII receptor MoAb IV.3. Immobilization of MoAb per se is insufficient to induce an activation signal because intact and F(ab′)2 fragments of nonstimulatory MoAb directed to glycoprotein lb and HLA class I do not become stimulatory when attached to beads. CD9-induced activation requires cytoskeletal rearrangement because it is inhibited by cytochalasin B. Aggregation is blocked by inhibitors of the thromboxane pathway, indicating that CD9 activates phospholipase C indirectly through prior activation of phospholipase A2.

Original languageEnglish (US)
Pages (from-to)1753-1759
Number of pages7
JournalBlood
Volume78
Issue number7
StatePublished - Oct 1 1991
Externally publishedYes

Fingerprint

Immobilized Antibodies
Platelet Activation
Platelets
Microspheres
Platelet Aggregation
Immobilization
Blood Platelets
Chemical activation
Monoclonal Antibodies
Immunoglobulin Fragments
Cytochalasin B
Agglomeration
Phospholipases A2
Thromboxanes
Type C Phospholipases
Goats
Glycoproteins
Antibodies
Latex
Immunoglobulin G

ASJC Scopus subject areas

  • Hematology

Cite this

Griffith, L., Slupsky, J., Seehafer, J., Boshkov, L., & Shaw, A. R. E. (1991). Platelet activation by immobilized monoclonal antibody: Evidence for a CD9 proximal signal. Blood, 78(7), 1753-1759.

Platelet activation by immobilized monoclonal antibody : Evidence for a CD9 proximal signal. / Griffith, Lee; Slupsky, Joseph; Seehafer, Jutta; Boshkov, Lynn; Shaw, Andrew R E.

In: Blood, Vol. 78, No. 7, 01.10.1991, p. 1753-1759.

Research output: Contribution to journalArticle

Griffith, L, Slupsky, J, Seehafer, J, Boshkov, L & Shaw, ARE 1991, 'Platelet activation by immobilized monoclonal antibody: Evidence for a CD9 proximal signal', Blood, vol. 78, no. 7, pp. 1753-1759.
Griffith L, Slupsky J, Seehafer J, Boshkov L, Shaw ARE. Platelet activation by immobilized monoclonal antibody: Evidence for a CD9 proximal signal. Blood. 1991 Oct 1;78(7):1753-1759.
Griffith, Lee ; Slupsky, Joseph ; Seehafer, Jutta ; Boshkov, Lynn ; Shaw, Andrew R E. / Platelet activation by immobilized monoclonal antibody : Evidence for a CD9 proximal signal. In: Blood. 1991 ; Vol. 78, No. 7. pp. 1753-1759.
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