title: CD 18 monoclonal antibody inhibits neutrophil diapedesis in the murine dermis induced by leukotriene B4 and 12(R)-hydroxyeicosatetraenoic acid.
abstract: Neutrophil accumulation is a hallmark of the inflammatory process. The ability of neutrophils to release lipid mediators, toxic oxygen metabolites, proteolytic enzymes and cationic proteins may contribute to the tissue pathology seen in inflammatory diseases such as inflammatory bowel disease and psoriasis. The first step in the process of neutrophil diapedesis in a gradient of chemoattraction is adhesion to the microvascular endothelium, a phenomenon mediated by the stimulated activation of the neutrophil CD11a-c/CD18 cell surface glycoprotein complex. We assessed the ability of a monoclonal antibody (MoAb) (hybridoma: SP2/0-Ag. 14XBALB/c spleen cells; isotype: murine IgG1) to CD18 that recognizes the beta chain of LFA1(CD11a/CD18), MAC-1(CD11b/CD18) and CD11c/CD18 to effect the neutrophils response to the proinflammatory chemotaxins leukotriene B4 (LTB4) and 12(R)-hydroxy-5,8,11,14-eicosatetraenoic acid [12(R)-HETE] in the mouse dermis. LTB4 and 12(R)-HETE induce a time and concentration dependent infiltration of s when applied intradermally. LTB4 (100 ng) and 12(R)-HETE (50 micrograms) were injected intradermally in CD-mice (18 g body weight) and assessed for chemotactic activity four h later by the dermal levels of myeloperoxidase (MPO), a neutrophil marker enzyme. CD18 MoAb(0.02 mg) was given intravenously 10 min ahead of dermal chemotaxin injection. LTB4 increased (p less than .01) dermal levels of MPO at 4 h, a neutrophil accumulation inhibited (p less than .005) by CD18 MoAb pretreatment (Mean MPO +/- SEM: Vehicle, 0.049 +/- 0.006U vs LTB4, 0.309 +/- 0.033U vs MoAb, 0.137 +/- 0.012U) (n = 12/group).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Gastrointestinal Diseases Research, Searle Research and Development, Skokie, IL 60077.
authors.forename: D
authors.initials: D
authors.lastname: Fretland
authors.forename: D
authors.initials: D
authors.lastname: Widomski
authors.forename: C
authors.initials: C
authors.lastname: Anglin
authors.forename: T
authors.initials: T
authors.lastname: Gaginella
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000276:immunology; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D002449:Cell Aggregation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D012867:Skin / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D018845:CD11 Antigens; D018821:CD18 Antigens; D006893:Hydroxyeicosatetraenoic Acids; D016028:Receptors, Leukocyte-Adhesion; D007975:Leukotriene B4