title: Demonstration of a novel circulating anti-prostacyclin receptor antibody.
abstract: Although coronary artery disease (CAD) is appreciated to be accelerated in patients with chronic spinal cord injury (SCI), the underlying mechanism of CAD in SCI remains obscure. We have recently shown that platelets from subjects with SCI develop resistance to the inhibitory effect of prostacyclin (PGI2) on the platelet stimulation of thrombin generation. The loss of the inhibitory effect was due to the loss of high-affinity prostanoid receptors, which may contribute to atherogenesis in SCI. Incubation of normal, non-SCI platelets in SCI plasma (n = 12) also resulted in the loss of high-affinity binding of PGI2 (Kd1 = 9.1 +/- 2.0 nM; n1 = 170 +/- 32 sites per cell vs. Kd1 = 7.2 +/- 1.1 nM; n1 = 23 +/- 8 sites per cell), with no significant change in the low-affinity receptors (Kd2 = 1.9 +/- 0.1 microM; n2 = 1,832 +/- 232 sites per cell vs. Kd2 = 1. 6 +/- 0.1 microM; n2 = 1,740 +/- 161 sites per cell) as determined by Scatchard analysis of the binding of [3H]PGE1. The loss of high-affinity PGI2 binding led to the failure of PGI2 to inhibit the platelet-stimulated thrombin generation. The increase of cellular cyclic AMP level, mediated through the binding of PGI2 to low-affinity receptors in platelets, was unaffected in SCI platelets. PAGE and immunoblot of SCI plasma showed the presence of an IgG band, which specifically blocked the binding of [3H]PGE1 to the high-affinity PGI2 receptors of normal platelets. PAGE of the reduced IgG band, the amino acid sequence of the novel band as a heavy chain of IgG that inhibits the binding of [3H]PGE1 to the high-affinity platelet PGI2 receptor, demonstrates that the specific recognition and inhibition of high-affinity PGI2 binding to platelets was due to an anti-prostacyclin receptor antibody present in SCI plasma.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: N N
authors.initials: NN
authors.lastname: Kahn
authors.forename: W A
authors.initials: WA
authors.lastname: Bauman
authors.forename: A K
authors.initials: AK
authors.lastname: Sinha
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood*; D001792:Blood Platelets / Q000276:immunology*; D003327:Coronary Disease / Q000209:etiology; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000276:immunology*; D013119:Spinal Cord Injuries / Q000097:blood / Q000150:complications / Q000276:immunology*
chemical_list: D000906:Antibodies; D010975:Platelet Aggregation Inhibitors; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D011464:Epoprostenol