Spontaneous Skin Ulceration and Defective T Cell Function in CD18 Null Mice

Abstract

A null mutation was prepared in the mouse for CD18, the β2 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.

The Virulence Function of Streptococcus pneumoniae Surface Protein A Involves Inhibition of Complement Activation and Impairment of Complement Receptor-Mediated Protection

“…Previous studies showed that CD18-deficient animals have increased spontaneous infections and earlier mortality compared with WT mice (33). Others reported that LFA-1 Ϫ/Ϫ mice have increased mortality and a higher incidence of otitis media.…”

Migration of immature mouse DC across resting endothelium is mediated by ICAM‐2 but independent of β2‐integrins and murine DC‐SIGN homologues

“…Schneeberger et al [41] found a partial reduction in the number of DC in the lungs of CD18-deficient mice, although it is not clear whether this is due to a defect in TEM itself or to spontaneous inflammation observed in such mice [32], which might lead to subsequent depletion of DC from inflamed organs. In contrast to the data from the lung model, Grabbe et al [42] observed no differences in the migration of CD18-deficient immature DC to the inflamed skin in a model of acute contact dermatitis.…”

“…We subsequently compared the TEM of immature DC derived from CD18-deficient 129Sv/C57BL/6 mice [32] with that of wild-type DC, obtained from their CD18-positive littermates. The different genetic background of these mice and the Balb/c mice used before had no effect on TEM since immature wild-type DC obtained from 129Sv/C57BL/6 and Balb/c mice neither showed significant differences in the absolute numbers of transmigrating cells (data not shown) nor in the relative numbers of cells transmigrating across monolayers of the three endothelial cell lines (compare Fig.…”

Structural and mechanical functions of integrins

“…Inappropriate activation of these integrins results in pathologies, such as bleeding disorders (Shattil and Ginsberg 1997;Shattil and Newman 2004;Petrich et al 2007). The β2 integrin subfamily found in leukocytes and T cells are also expressed in the inactive state (Scharffetter-Kochanek et al 1998;Baker and Koretzky 2008). Upon activation by cytokines, these receptors bind their ligands and facilitate adhesion to facilitate inflammation, cytotoxic killing, phagocytosis or lymphocyte recruitment (Rosenkranz and Mayadas 1999).…”