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J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/10/1357/08 $2.00
Volume 186, Number 8, October 20, 1997 1357-1364

Neutrophil Emigration in the Skin, Lungs, and Peritoneum: Different Requirements for CD11/CD18 Revealed by CD18-deficient Mice

By Joseph P. Mizgerd,* Hiroshi Kubo,* Gregory J. Kutkoski,* Sabrina D. Bhagwan,* Karin Scharffetter-Kochanek,Dagger Arthur L. Beaudet,Dagger and Claire M. Doerschuk*

From the * Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; and Dagger  Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030

To determine the role of CD11/CD18 complexes in neutrophil emigration, inflammation was induced in the skin, lungs, or peritoneum of mutant mice deficient in CD18 (CD18-/- mutants). Peripheral blood of CD18-/- mutants contained 11-fold more neutrophils than did blood of wild-type (WT) mice. During irritant dermatitis induced by topical application of croton oil, the number of emigrated neutrophils in histological sections of dermis was 98% less in CD18-/- mutants than in WT mice. During Streptococcus pneumoniae pneumonia, neutrophil emigration in CD18-/- mutants was not reduced. These data are consistent with expectations based on studies using blocking antibodies to inhibit CD11/CD18 complexes, and on observations of humans lacking CD11/CD18 complexes. The number of emigrated neutrophils in lung sections during Escherichia coli pneumonia, or in peritoneal lavage fluid after 4 h of S. pneumoniae peritonitis, was not reduced in CD18-/- mutants, but rather was greater than the WT values (240 ± 30 and 220 ± 30% WT, respectively). Also, there was no inhibition of neutrophil emigration during sterile peritonitis induced by intraperitoneal injection of thioglycollate (90 ± 20% WT). These data contrast with expectations. Whereas CD11/CD18 complexes are essential to the dermal emigration of neutrophils during acute dermatitis, CD18-/- mutant mice demonstrate surprising alternative pathways for neutrophil emigration during pneumonia or peritonitis.


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