title: Neutrophil adhesion in leukocyte adhesion deficiency syndrome type 2.
abstract: We have previously reported a newly discovered congenital disorder of neutrophil adhesion, leukocyte adhesion deficiency syndrome type 2 (LAD II). The clinical manifestations of this syndrome are similar to those seen in the classic leukocyte adhesion deficiency syndrome, now designated type 1 (LAD I), but the two syndromes differ in the molecular basis of their adhesion defects. LAD I is caused by a deficiency in the CD18 integrin adhesion molecules while LAD II patients are deficient in expression of sialyl-Lewis X (SLeX), a carbohydrate ligand for selectins. In this report we demonstrate that neutrophils from a LAD II patient bind minimally or not at all to recombinant E-selectin, purified platelet P-selectin, or P-selectin expressed on histamine-activated human umbilical vein endothelial cells, but have normal levels of L-selectin and CD11b/CD18 integrin, and adhere to and migrate across endothelium when CD11b/CD18 is activated. We compare LAD I and LAD II patient neutrophil function in vitro, demonstrating that integrin and selectin adhesion molecules have distinct but interdependent roles in neutrophil adhesion during an inflammatory response.
authors.affiliation: Cytel Corporation, San Diego, California 92121, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Phillips
authors.forename: B R
authors.initials: BR
authors.lastname: Schwartz
authors.forename: A
authors.initials: A
authors.lastname: Etzioni
authors.forename: R
authors.initials: R
authors.lastname: Bayer
authors.forename: H D
authors.initials: HD
authors.lastname: Ochs
authors.forename: J C
authors.initials: JC
authors.lastname: Paulson
authors.forename: J M
authors.initials: JM
authors.lastname: Harlan
mesh_terms: D018845:CD11 Antigens / Q000502:physiology; D018821:CD18 Antigens / Q000502:physiology; D002448:Cell Adhesion; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D019040:E-Selectin / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000097:blood* / Q000145:classification; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology; D011336:Probability; D012016:Reference Values; D014471:Umbilical Veins
chemical_list: D018845:CD11 Antigens; D018821:CD18 Antigens; D019040:E-Selectin; D019007:P-Selectin