title: Spontaneous skin ulceration and defective T cell function in CD18 null mice.
abstract: A null mutation was prepared in the mouse for CD18, the beta2 subunit of leukocyte integrins. Homozygous CD18 null mice develop chronic dermatitis with extensive facial and submandibular erosions. The phenotype includes elevated neutrophil counts, increased immunoglobulin levels, lymphadenopathy, splenomegaly, and abundant plasma cells in skin, lymph nodes, gut, and kidney. Very few neutrophils were found in spontaneously occurring skin lesions or with an induced toxic dermatitis. Intravital microscopy in CD18 null mice revealed a lack of firm neutrophil attachment to venules in the cremaster muscle in response to N-formyl- methionyl-leucyl-phenylalanine. A severe defect in T cell proliferation was found in the CD18 null mice when T cell receptors were stimulated either by staphylococcal enterotoxin A or by major histocompatibility complex alloantigens demonstrating a greater role of CD11/CD18 integrins in T cell responses than previously documented. The null mice are useful for delineating the functions of CD18 in vivo.
authors.affiliation: Department of Molecular and Human Genetics, Houston, Texas 77030, USA.
authors.forename: K
authors.initials: K
authors.lastname: Scharffetter-Kochanek
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.forename: K
authors.initials: K
authors.lastname: Norman
authors.forename: N
authors.initials: N
authors.lastname: van Nood
authors.forename: F
authors.initials: F
authors.lastname: Munoz
authors.forename: S
authors.initials: S
authors.lastname: Grabbe
authors.forename: M
authors.initials: M
authors.lastname: McArthur
authors.forename: I
authors.initials: I
authors.lastname: Lorenzo
authors.forename: S
authors.initials: S
authors.lastname: Kaplan
authors.forename: K
authors.initials: K
authors.lastname: Ley
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
authors.forename: C A
authors.initials: CA
authors.lastname: Montgomery
authors.forename: S
authors.initials: S
authors.lastname: Rich
authors.forename: A L
authors.initials: AL
authors.lastname: Beaudet
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000235:genetics* / Q000502:physiology; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000494:pharmacology; D006651:Histocytochemistry; D006801:Humans; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016897:Respiratory Burst / Q000235:genetics; D012883:Skin Ulcer / Q000235:genetics*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D018821:CD18 Antigens; D004768:Enterotoxins; D011948:Receptors, Antigen, T-Cell; C026066:enterotoxin A, Staphylococcal; D015054:Zymosan