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Role of prostaglandin synthesis in rabbit platelet activation initiated by basophil derived platelet activating factor (PAF)
PROSTAGLANDINS
Role of Prostaglandin Synthesis in Rabbit Platelet Activation Initiated by Basophil Derived Platelet Activating Factor (PAF) James 0. Shaw, Morton Printz, Roger Stewart, Peter Henson Scripps Clinic and Research Foundation, La Jolla, California Department of Medicine, University of California, San Diego, Ca. ABSTRACT This study was designed to determine the importance of pla+'-{ let prostaglandin synthesis in the initiation of rabbit platelet-.,. aggregation and secretion induced by PAF and other platelet stim-', uli. Platelet prostaglandin (PG) content was determined by radi‘oirmnunoassay for PGE and PGFsa with endoperoxides measured as PGF2c after reduction with SnCl2. PG levels were measured in platelets activated with stimulus-doses giving approximately 70% 3%serotonin (5-I-W.) secretion. Substantial PG production was observed with collagen, PAF, and arachidonic acid (AA) as stimuli. Thranbin and 1gG anti-platelet antibody ("PIAB) induced smaller, barely significant increases in platelet PG levels. Kinetic studies revealed that with PAF, like collagen and AA, but not thrombin or CIPIAB, endoperoxide production preceeded secretion of 5-IiT and ADP. The cycle-oxygenase inhibitors, aspirin and indomethacin, inhibited PAF induced 5-HT secretion only at low stimulus concentrations. However, platelet secretion caused by collagen and AA was markedly attenuated by these compounds. Similarly, concentrations of aspirin and indomethacin, which completely abolished platelet aggregation caused by AA and collagen, failed to affect PAF initiated aggregation. PAF is a unique platelet stimulus which, although having the capacity to stimulate platelet PG production, can activate platelets independent of the PG pathway. (Supported by HL 05229 and HL17786) Antibody-Dependent Initiation of Bone Resorption by Complement and Its Mediation by Prostaglandins A.L. Sandberg, L.G. Raise, H.A. Simmons, J.M. Goodson, S.E. Mergenhagen Laboratory of Microbiology and Immunology, NIDR, NIH, Bethesda,Md. Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut 06032 University of California School of Dentistry, San Francisco,Ca. 94122 ABSTRACT Activation of the complement (C) system stimulated the synthesis of prostaglandin E with resultant bone resorption as quantitated by the release of 45Ca from organ cultures of fetal rat bones (radii and ulnae) labeled in utero. Heating the rabbit serun which served as the C source maxedlyeduced its bone resorptive capacity. The late C components, at least through C6, were required since serum from rabbits genetically lacking C6 failed to support bone resorption. Addition of functionally purified C6 restored resorptive activity to the C6 deficient serum. Immunoglobulins reactive with cell surface antigens initiated the C activation. The normal rabbit serum contained "natural antibody" which agglutinated rat erythrocytes. Absorp-
1020
JUNE 1977 VOL. 13 NO. 6
Role of Prostaglandin Synthesis in Rabbit Platelet Activation Initiated by Basophil Derived Platelet Activating Factor (PAF) James 0. Shaw, Morton Printz, Roger Stewart, Peter Henson Scripps Clinic and Research Foundation, La Jolla, California Department of Medicine, University of California, San Diego, Ca. ABSTRACT This study was designed to determine the importance of pla+'-{ let prostaglandin synthesis in the initiation of rabbit platelet-.,. aggregation and secretion induced by PAF and other platelet stim-', uli. Platelet prostaglandin (PG) content was determined by radi‘oirmnunoassay for PGE and PGFsa with endoperoxides measured as PGF2c after reduction with SnCl2. PG levels were measured in platelets activated with stimulus-doses giving approximately 70% 3%serotonin (5-I-W.) secretion. Substantial PG production was observed with collagen, PAF, and arachidonic acid (AA) as stimuli. Thranbin and 1gG anti-platelet antibody ("PIAB) induced smaller, barely significant increases in platelet PG levels. Kinetic studies revealed that with PAF, like collagen and AA, but not thrombin or CIPIAB, endoperoxide production preceeded secretion of 5-IiT and ADP. The cycle-oxygenase inhibitors, aspirin and indomethacin, inhibited PAF induced 5-HT secretion only at low stimulus concentrations. However, platelet secretion caused by collagen and AA was markedly attenuated by these compounds. Similarly, concentrations of aspirin and indomethacin, which completely abolished platelet aggregation caused by AA and collagen, failed to affect PAF initiated aggregation. PAF is a unique platelet stimulus which, although having the capacity to stimulate platelet PG production, can activate platelets independent of the PG pathway. (Supported by HL 05229 and HL17786) Antibody-Dependent Initiation of Bone Resorption by Complement and Its Mediation by Prostaglandins A.L. Sandberg, L.G. Raise, H.A. Simmons, J.M. Goodson, S.E. Mergenhagen Laboratory of Microbiology and Immunology, NIDR, NIH, Bethesda,Md. Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut 06032 University of California School of Dentistry, San Francisco,Ca. 94122 ABSTRACT Activation of the complement (C) system stimulated the synthesis of prostaglandin E with resultant bone resorption as quantitated by the release of 45Ca from organ cultures of fetal rat bones (radii and ulnae) labeled in utero. Heating the rabbit serun which served as the C source maxedlyeduced its bone resorptive capacity. The late C components, at least through C6, were required since serum from rabbits genetically lacking C6 failed to support bone resorption. Addition of functionally purified C6 restored resorptive activity to the C6 deficient serum. Immunoglobulins reactive with cell surface antigens initiated the C activation. The normal rabbit serum contained "natural antibody" which agglutinated rat erythrocytes. Absorp-
1020
JUNE 1977 VOL. 13 NO. 6