Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan-polysaccharide (PG-PS)-induced arthritis.
Bradykinin (BK), a vasoactive, proinflammatory nonapeptide, promotes cell adhesion molecule (CAM) expression, leukocyte sequestration, inter-endothelial gap formation, and protein extravasation in postcapillary venules. These effects are mediated by bradykinin-1 (B1R) and-2 (B2R) receptors. We delineated some of the mechanisms by which BK could influence chronic inflammation by altering CAM expression on leukocytes, endothelium, and synovium in joint sections of peptidoglycan-polysaccharide-injected Lewis rats. Blocking B1R results in significantly increased joint inflammation. Immunohistochemistry of the B1R antagonist group revealed increased leukocyte and synovial CD11b and CD54 expression and increased CD11b and CD44 endothelial expression. B2R antagonism decreased leukocyte and synovial CD44 and CD54 and endothelial CD11b expression. Although these findings implicate B2R involvement in the acute phase of inflammation by facilitating leukocyte activation (CD11b), homing (CD44), and transmigration (CD54). Treatment with a B2R antagonist did not affect the disease evolution in this model. In contrast, when both BK receptors are blocked, the aggravation of inflammation by B1R blockade is neutralized and there is no difference from the disease-untreated model. Our findings suggest that B1R and B2R signaling show physiologic antagonism. B1R signaling suggests involvement in down-regulation of leukocyte activation, transmigration, and homing. Further studies are needed to evaluate the B1 receptor agonist's role in this model.
The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
I M
IM
Sainz
A B
AB
Uknis
I
I
Isordia-Salas
R A
RA
Dela Cadena
R A
RA
Pixley
R W
RW
Colman
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D039481:CD11b Antigen / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D019041:L-Selectin / Q000096:biosynthesis / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010457:Peptidoglycan / Q000633:toxicity; D011288:Prekallikrein / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D043783:Receptor, Bradykinin B1 / Q000502:physiology; D043782:Receptor, Bradykinin B2 / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D013583:Synovial Membrane / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
C121350:B 9858; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D039481:CD11b Antigen; C107323:CP 0597; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D009842:Oligopeptides; D010457:Peptidoglycan; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D011288:Prekallikrein; D001920:Bradykinin