Thromboxane mediates diapedesis after ischemia by activation of neutrophil adhesion receptors interacting with basally expressed intercellular adhesion molecule-1.
Ischemic injury is characterized by neutrophil (PMN)--endothelial cell adhesion and diapedesis associated with thromboxane (TX) generation. Neutrophil-endothelial cell interaction is regulated in part by the leukocyte adhesion receptor CD 18 glycoprotein complex and the endothelial intercellular adhesion molecule-1 (ICAM-1). This study tests the role of TX in ischemia-induced diapedesis and evaluates whether the diapedesis is regulated by neutrophil or endothelial adhesion receptors. Plasma derived from rabbit hind limbs made ischemic for 3 hours (n = 6) and reperfused for 10 minutes had increased levels of TXB2 3,450 pg/ml, which was higher than sham rabbit (n = 6) values of 653 pg/ml (p less than 0.05). When introduced into abraded skin chambers placed on the dorsum of other normal rabbits (n = 6), this ischemic plasma induced 1,000 pg/ml of new TX synthesis and diapedesis of 1,235 PMN/mm3. The total TX concentration and PMN accumulations in blister fluid were correlated (r = 0.88, p less than 0.05). In contrast, sham rabbit plasma induced no TX synthesis and diapedesis of only 77 PMN/mm3 (p less than 0.05). Administration of 50 ng/ml of authentic TXB2 into blisters induced an accumulation of 453 PMN/mm3, which was higher than that in saline controls (18 PMN/mm3) (p less than 0.05). Pretreatment of normal rabbits used for the diapedesis assay (n = 4) with the TX synthetase inhibitor OKY 046 (2 mg/kg/hr) limited ischemic plasma and authentic TXB2 induced diapedesis to 142 and 76 PMN/mm3, respectively (both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Goldman
G
G
Department of Surgery, Brigham and Women's Hospital, Boston, Mass.
Welbourn
R
R
Klausner
J M
JM
Valeri
C R
CR
Shepro
D
D
Hechtman
H B
HB
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018821:CD18 Antigens; D002196:Capillaries / Q000502:physiology / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003609:Dactinomycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009132:Muscles / Q000098:blood supply; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012039:Regional Blood Flow; D015424:Reperfusion; D012867:Skin / Q000098:blood supply; D013929:Thromboxane B2 / Q000097:blood / Q000494:pharmacology / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000502:physiology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D008689:Methacrylates; D016028:Receptors, Leukocyte-Adhesion; D013931:Thromboxanes; D018799:Intercellular Adhesion Molecule-1; D003609:Dactinomycin; D013929:Thromboxane B2; C045749:SQ 29548; D013930:Thromboxane-A Synthase; C034364:ozagrel