PMID- 8453097
OWN - NLM
STAT- MEDLINE
DCOM- 19930416
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 81
IP  - 6
DP  - 1993 Mar 15
TI  - Membrane glycoproteins and platelet cytoskeleton in immune complex-induced 
      platelet activation.
PG  - 1505-12
AB  - To clarify the mechanism of platelet activation by immune complexes and the 
      possible involvement of surface glycoproteins (GPs), we studied platelet 
      activation induced by heat-aggregated IgG (HAG). We examined the effects of 
      monoclonal antibodies (MoAbs) against GPIb, GPIIb/IIIa, and the Fc receptor on 
      resting platelets and on platelets stimulated by HAG. HAG increased the cytosolic 
      ionized calcium concentration ([Ca2+]i) and stimulated protein (P47 and P20) 
      phosphorylation, phosphatidic acid (PA) synthesis, serotonin secretion, and 
      platelet aggregation. IV.3, an anti-Fc gamma RII receptor MoAb, inhibited HAG 
      binding to platelets and all subsequent platelet responses. Like IV.3, MoAbs 
      against GPIIb/IIIa (Tab, 10E5, AP-3) or GPIb (AP-1, 6D1) strongly inhibited 
      platelet activation by HAG. However, while anti-GPIIb/IIIa MoAbs inhibited 
      binding of IV.3 and HAG to platelets, anti-GPIb MoAbs had little effect on 
      platelet binding of IV.3 or HAG. These observations suggest a close topographical 
      and functional association of GPIIb/IIIa with Fc gamma RII in the platelet 
      response to HAG. Cytochalasin B, an inhibitor of actin polymerization, also 
      inhibited platelet activation but not HAG or IV.3 binding. Measurement of the 
      fluorescence of 7-nitrobenz-2-oxa-1,3-(NBD)-phallacidin, a specific marker for 
      filamentous actin (F-actin), showed that both cytochalasin B and AP-1 blocked the 
      increase of F-actin induced by HAG. The common effects of anti-GPIb MoAbs and of 
      cytochalasin B suggest that unlike the activity of GPIIb/IIIa, the ability of 
      anti-GPIb to inhibit the activation of platelets by immune complexes is 
      associated with perturbation of the cytoskeleton.
FAU - Kang, J
AU  - Kang J
AD  - Department of Surgery, Beth Israel Hospital, Harvard Medical School, Boston, MA 
      02215.
FAU - Cabral, C
AU  - Cabral C
FAU - Kushner, L
AU  - Kushner L
FAU - Salzman, E W
AU  - Salzman EW
LA  - eng
GR  - HL-33014/HL/NHLBI NIH HHS/United States
GR  - HL-37610/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Platelet Membrane Glycoproteins)
RN  - 57576-52-0 (Thromboxane A2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - Antigen-Antibody Complex/*immunology
MH  - Calcium/metabolism
MH  - Cytoskeleton/*physiology
MH  - Humans
MH  - Immunoglobulin G/immunology
MH  - *Platelet Activation
MH  - Platelet Aggregation
MH  - Platelet Membrane Glycoproteins/*physiology
MH  - Thromboxane A2/physiology
EDAT- 1993/03/15 00:00
MHDA- 1993/03/15 00:01
CRDT- 1993/03/15 00:00
PHST- 1993/03/15 00:00 [pubmed]
PHST- 1993/03/15 00:01 [medline]
PHST- 1993/03/15 00:00 [entrez]
AID - S0006-4971(20)74698-7 [pii]
PST - ppublish
SO  - Blood. 1993 Mar 15;81(6):1505-12.